The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index; 8 of the 37 sources its claims cite were checked for support.
Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis
Open accessAbstract
Clathrin-mediated endocytosis of surface receptors and their bound ligands (i.e., cargo) is highly regulated, including by the cargo itself. One of the possible sources of the observed heterogeneous dynamics of clathrin-coated pits (CCPs) might be the different cargo content. Consistent with this, we show that CCP size and dynamic behavior varies with low density lipoprotein receptor (LDLR) expression levels in a manner dependent on the LDLR-specific adaptors, Dab2 and ARH. In Dab2-mCherry–expressing cells, varying LDLR expression leads to a progressive increase in CCP size and to the appearance of nonterminal endocytic events. In LDLR and ARH-mCherry–expressing cells in addition to an increase in CCP size, turnover of abortive CCPs increases, and the rate of CCP maturation decreases. Altogether, our results underscore the highly dynamic and cargo-responsive nature of CCP assembly and suggest that the observed heterogeneity is, in part, related to compositional differences (e.g., cargo and adaptors) between CCPs.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In BSC1 cells, LDLR cargo and its adaptors Dab2 and ARH regulate clathrin-coated pit (CCP) size and dynamics in cargo- and adaptor-specific ways. Dab2 can drive formation of large, endocytically inactive clathrin lattices, whereas ARH is AP2-dependent, partially rescues saturated CD8/LDLR uptake, and increases cargo packaging without speeding productive CCP maturation.
Key findings
- CCP size varied with CD8/LDLR and adaptor expression: negative-stain EM ventral CCP area was 0.013 ± 0.03 µm² with no CD8/LDLR, 0.45 ± 0.38 µm² at low CD8/LDLR, 3.31 ± 2.49 µm² at high CD8/LDLR with Dab2, and 0.89 ± 0.54 µm² at high CD8/LDLR with ARH (Table I). TfnR overexpression on the dorsal surface gave smaller CCPs than control (0.008 ± 0.003 vs. 0.011 ± 0.004 µm²).
- Dab2 and ARH were differentially recruited: ARH was predominantly nuclear under control conditions, exited the nucleus upon CD8/LDLR expression, and required AP2 binding for CCP recruitment; ARH-F259A failed to bind AP2 and was not recruited to CCPs, while ARH-S117Y;F165A failed to exit the nucleus.
- ARH partially rescued saturated CD8/LDLR endocytosis in an AP2-dependent manner: ARH-252A255 only slightly increased uptake efficiency, ARH-F259A had no effect, and µ2 siRNA knockdown ablated the rescue. TfnR uptake was not rescued by ARH.
- CD8/LDLR overexpression reduced the productive CCP contribution from 50.7 ± 2.0% to 41.3 ± 2.1% and increased productive CCP lifetime from 62.8 ± 3.1 s to 75.5 ± 5.0 s; added ARH did not alter productive lifetime (76.3 ± 5.2 s). Abortive CCP initiation increased from 0.29 ± 0.071 to 0.41 ± 0.093 pits/min/µm² with CD8/LDLR, while productive CCP initiation remained ~0.088–0.089 pits/min/µm².
Methods
- BSC1 cells stably expressing LCa-EGFP or σ2-EGFP were infected with tet-repressible CD8/LDLR adenovirus and transfected or selected for wild-type or mutant Dab2/ARH constructs; assays included TIR-FM, spinning-disk confocal FRAP, negative-stain EM of unroofed ventral membranes, cell fractionation/Western blotting, and anti-CD8 internalization ELISA.
- CCP dynamics were analyzed by automated particle detection and lifetime tracking, with CCP subpopulations classified as early abortive, late abortive, productive, and persistent; intensity profiles were averaged for CCP cohorts by lifetime.
- Statistical comparisons used jackknifed cell-to-cell errors, Kolmogorov-Smirnov tests, and reported P values; CCP trajectory numbers included 100,823 control, 70,955 CD8/LDLR, and 23,394 CD8/LDLR + ARH trajectories.
Limitations
- The paper states that CD8/LDLR clustering could not be followed directly because overexpression strongly decreased the plasma-membrane signal-to-noise ratio, impeding automated tracking of cargo-laden CCPs.
- The paper states that ARH nuclear shuttling and possible nuclear function are beyond the scope of the study, and that additional studies are required to determine mechanisms controlling clathrin polymerization.
- Evident from the text: most experiments use BSC1 cells with exogenous CD8/LDLR chimeras and overexpressed or mutant adaptors, so findings may not directly reflect native LDLR trafficking or other cell types; the checkpoint hypothesis is proposed but not fully tested.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
8 of 37 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Together, these data strongly suggest that the observed heterogeneity in the dynamic behavior of CCPs (Merrifield et al., 2005; Rappoport et al., 2005; Yarar et al., 2005) could reflect differences in their content of cargo and adaptor molecules.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion
What the sources say
- Not checked — no full text of the sourcecites Merrifield et al., 2005 source
- Supportedcites Rappoport et al., 2005 source
The citation is attached to the observed heterogeneity in CCP dynamics, rather than to the citing authors’ subsequent explanation for it. The Abstract describes static, appearing, laterally moving, and disappearing clathrin spots; the Results and Discussion also distinguish static from disappearing spots by AP-2 content. No page number is available in our copy. (LLM, conf=0.92)
- Supportedcites Yarar et al., 2005 source
In “F-actin Is Associated with Several Diverse Behaviors of CCSs,” the paper reports heterogeneous behaviors, including splitting, coalescence, and movement at different speeds. “CCS Lateral Motility and Actin Dynamics” further suggests that laterally mobile structures may differ from those undergoing internalization in molecular composition, particularly cargo-adaptor content. These passages support the cited possibility; the citing authors’ broader conclusion is their own framing. (LLM, conf=0.91)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“it appears to sort cargo into CCPs independently of AP2 (Garuti et al., 2005; Keyel et al., 2006; Maurer and Cooper, 2006).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Introduction
What the sources say
- Partly supportedcites Garuti et al., 2005 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says Dab-2 may assist LDLR internalization, supporting a possible role in cargo uptake. But the experiments showing LDLR clustering despite disruption of an AP-2 binding site concern ARH, not Dab2; this copy does not establish that Dab2 acts independently of AP-2. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites Keyel et al., 2006 source
- Not checked — no full text of the sourcecites Maurer and Cooper, 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The incorporation of certain cargo/adaptor protein complexes (i.e., transferrin receptor/AP2) into CCPs increases the efficiency of CCP maturation without affecting CCP density or CCP maturation rate (Loerke et al., 2009; Mettlen et al., 2009).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Introduction
What the sources say
- Partly supportedcites Loerke et al., 2009 sourceExperimental — accuracy not yet measured
The Results section, “Cargo Concentration Enhances CCP Maturation Efficiency” (page unavailable), reports that TfnR overexpression increased the productive fraction of CCPs in an AP2-dependent manner and concludes that TfnR is not rate-limiting for vesicle formation. But the productive CCP lifetime decreased slightly in one measured condition, and the available Figure 3 caption identifies a pit-density comparison without stating that density was unchanged. Those unqualified parts of the claim are not fully supported by our copy. (LLM, conf=0.85)
- Partly supportedcites Mettlen et al., 2009 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says CCP maturation is sensitive to cargo loading, supporting the general link between cargo incorporation and maturation. It does not report that transferrin receptor/AP-2 incorporation increases maturation efficiency without changing pit density or maturation rate. The Results (page unavailable) instead report that AP-2 depletion reduced the number of CCPs while leaving the proportions and lifetimes of CCP subpopulations unchanged; depletion is not the same manipulation as incorporation. (LLM, conf=0.85)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We previously identified an endocytic restriction/checkpoint and provided evidence that progression beyond the checkpoint (i.e., CCP maturation efficiency) was enhanced by TfnR overexpression in a manner dependent on AP2 adaptors (Loerke et al., 2009).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
What the sources say
- Supportedcites Loerke et al., 2009 source
The Discussion proposes an endocytosis checkpoint or restriction point and identifies cargo-enhanced maturation as dependent on, or limited by, AP2 adaptor concentration. The Results sections report that TfnR overexpression increased the productive CCP population, whereas it did not do so in AP2-depleted cells. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dab2-mCherry colocalized with enhanced GFP (EGFP)–tagged clathrin light chain a (LCa-EGFP; Fig. 1, A–C) and EGFP-tagged σ2 subunit of AP2 (σ2-EGFP; Fig. S2 A) in CCPs at the cell surface.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Under these conditions, ARH partially displaces AP2 from CCPs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In cells expressing CD8/LDLR, ARH-mCherry displayed nearly identical accumulation kinetics during the first 30–40 s at CCPs as compared with LCa-EGFP (Fig. 8 D, orange lines vs. green lines, respectively).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, if we first expressed CD8/LDLR for 2–7 h and then added LmB, ARH redistributed from the nucleus to CCPs (Fig. S3 Fb,c).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > AP2 binding is required for CCP recruitment of ARH, whereas its nuclear export is passive and AP2 independent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the effect of CD8/LDLR overexpression on CCP dynamics was relatively small.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(ii) ARH, which is lacking NPF motifs, did not induce formation of flat lattices”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ARH translocated from the nucleus into the cytosol upon CD8/LDLR expression”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(i) the strong colocalization of these various adaptors in CCPs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, we found that ARH expression induced strong membrane recruitment of AP2 even in the absence of CD8/LDLR overexpression (Fig. 5 D, µ2 signal)”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH stabilized AP2 at the plasma membrane
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, we were also able to detect a small fraction of “nonterminal” events (Fig. 3 A, arrowhead at 140 s)”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Dab2 and CD8/LDLR expression can induce clathrin-coated structures (CCSs) that mimic nonterminal endocytic events
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At very high levels of CD8/LDLR overexpression, Dab2 induced the formation of large, flat, and endocytically inactive clathrin lattices on the ventral cell surface.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“With increasing expression levels of CD8/LDLR, the efficiency of CME decreased (Fig. 6 A).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH partially rescues saturated CME in an AP2-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, in our studies, CCPs detected by EM on the dorsal surface of BSC1 cells overexpressing TfnR alone were smaller than in control cells (Table I).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the endocytic efficiency of CD8/LDLR uptake under high (0 ng/ml tet) expression levels was increased in cells expressing an additional pool of ARH (Fig. 6, B and C; open symbols/bars).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH partially rescues saturated CME in an AP2-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The fact that both Dab2 and ARH increased the size of CCPs relative to CCPs in which AP2 is the predominant adaptor (i.e., under conditions of TfnR overexpression)”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“At very high levels of expression, most of the CD8/LDLRs are diffusely distributed on the plasma membrane and not captured in CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“(iii) the displacement of AP2 by ARH from cargo-laden CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Clathrin-coated pit size and dynamic behavior varies with low density lipoprotein receptor (LDLR) expression levels in a manner dependent on the LDLR-specific adaptors, Dab2 and ARH.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In agreement with previous studies (Morris and Cooper, 2001; Keyel et al., 2006; Maurer and Cooper, 2006; Chetrit et al., 2009), we observed colocalization of exogenously expressed mCherry-labeled Dab2 with clathrin-coat components in control cells.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistent with this, CD8/LDLR overexpression alone does not significantly alter overall CCP density (Fig. S4 A).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH stabilized AP2 at the plasma membrane
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(i) Dab2-p67, which is unable to bind clathrin and AP2 but contains NPF motifs, was able to induce the formation of GCCSs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“increased LDLR/ARH levels led to a slight increase in the initiation, turnover rate, and number of abortive CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At endogenous levels of cargo, we observed an increase in the number of nonterminal endocytic events”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Under the same experimental conditions, ARH displayed a fundamentally distinct intracellular distribution: it was predominantly nuclear with only a barely detectable recruitment to CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Even in the absence of exogenously expressed cargo, the strong membrane recruitment of this protein alone was sufficient to induce GCCSs (Fig. 2 Aa)”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Increased membrane recruitment of Dab2 is sufficient to induce GCCSs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“overexpression of CD8/LDLR increased the recruitment of both Dab2 and ARH to the plasma membrane.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Surprisingly, in cells overexpressing CD8/LDLRs in either the absence or presence of an additional pool of ARH, the relative contribution of productive CCPs decreased to 41.3 ± 2.1% and 44.5 ± 2.2%, respectively (Fig. 7 A).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“slows the rate of CCP maturation”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unlike Dab2, the combined presence of ARH and CD8/LDLR did not induce formation of GCCSs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Like LCa-EGFP and ARH-mCherry, AP2 rapidly accumulated in CCPs (Fig. 8 E, blue lines).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our live-cell and electron microscopy experiments demonstrated that this is accomplished, in part, by a prolonged growth phase and increased size of individual CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“To establish the specificity of this effect, we showed that TfnR uptake, which was also saturated upon its overexpression, was not rescued by ARH (Fig. S1 C).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH partially rescues saturated CME in an AP2-dependent manner
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and increases the size of CCPs through membrane recruitment of its specific adaptors, Dab2 and ARH.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, we show here that overexpression of another constitutively internalized cargo, the LDLR, increases the rate of initiation and turnover of abortive CCPs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Expression of an additional pool of ARH in the presence of CD8/LDLR reduced the amount of σ2-EGFP per CCP (Fig. 8, E and F; green lines and bars, respectively).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the average lifetime of late abortive structures was decreased from 19.1 ± 1.7 s under control conditions to 17.2 ± 1.2 s in the presence of CD8/LDLRs and further decreased to 15.5 ± 0.8 s upon expression of ARH (Fig. 7 B).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“To our surprise, unlike the identically labeled Dab2, the vast majority of ARH-mCherry was found in the nucleus of BSC1 cells (Fig. 3, A and B).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we have taken care to select stable transformants expressing low levels of ARH-mCherry and show biochemically that ARH is able to increase the efficiency of LDLR uptake at saturation.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, we observed a cargo and adaptor expression-dependent continuum in regulating the size of CCPs, such that TfnR overexpression < control cells = Dab2 alone < CD8/LDLR overexpression alone < low CD8/LDLR + Dab2 < high CD8/LDLR + ARH ≪ high CD8/LDLR + Dab2.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the average lifetime of productive CCPs, which reflects the rate of maturation, increased significantly from 62.8 ± 3.1 s to 75.5 ± 5.0 s upon CD8/LDLR overexpression (Fig. 7 B).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In cells expressing Dab2-mCherry, the size of CCPs increased with increasing levels of CD8/LDLR expression.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results show that nuclear exit of ARH is passive and suggest the existence of a second PTB domain binding partner required for nuclear import of ARH.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > AP2 binding is required for CCP recruitment of ARH, whereas its nuclear export is passive and AP2 independent
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, these results demonstrate that saturated CME can be partially accounted for by a limited amount of adaptor proteins.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH partially rescues saturated CME in an AP2-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that the relative amounts of ARH and AP2 define the size (i.e., the intensities) of diffraction-limited CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Previously, it has been reported that constitutive CME is saturable (Warren et al., 1997, 1998; Loerke et al., 2009).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH partially rescues saturated CME in an AP2-dependent manner
What the sources say
- Not checked yetcites Warren et al., 1997 source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites Warren et al., 1998 source
- Not checked yetcites Loerke et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“That these kinetics were less affected by CD8/LDLR overexpression argues that reduced CME efficiency under these conditions reflects saturation of adaptor-dependent recruitment of cargo into CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The efficiency of CME depends on cargo loading/concentration into CCPs.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This expected localization of Dab2-mCherry suggests that the fluorescent tag did not interfere with its function.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, CCPs that take longer to pinch off have a higher ratio of clathrin:ARH than shorter-lived CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The presence or absence of a variable fraction of nonterminal events in different cell types could be explained by variable amounts of cargo and/or Dab2 at the plasma membrane.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Similar GCCSs have been observed in other cell types upon Dab-2 overexpression, associated with integrins, another Dab2-specific cargo molecule (Chetrit et al., 2009).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
What the sources say
- Not checked — no full text of the sourcecites Chetrit et al., 2009 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“recruitment of the LDLR relies on an FXNPXY motif (Davis et al., 1986) recognized by the adaptors Dab2 and ARH.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Introduction
What the sources say
- Not checked — no full text of the sourcecites Davis et al., 1986 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, GCCS formation is likely dependent on levels of expression of Dab2 and endogenous cargo.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Dab2 is recruited to CCPs and can function independently of AP2.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altogether, these data clearly establish the requirement of AP2 for ARH-mediated LDLR uptake, which mirrors the requirements for ARH targeting to CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH partially rescues saturated CME in an AP2-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data indicate that despite the dependence of ARH on AP2, these adaptors nonetheless also compete for incorporation into CCPs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Recently, based on lifetime decomposition, we identified three CCP subpopulations, termed early abortive, late abortive, and productive CCPs (Loerke et al., 2009).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Introduction
What the sources say
- Not checked yetcites Loerke et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Instead, it occurred through an increased efficiency of LDLR sorting/packaging into CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“might reflect the need to accommodate the very large ligands bound by LDLR and LRP (Jones et al., 2003) (i.e., LDL particles, d∼22 nm and α2-macroglobulin, d∼18.5 nm; Krimbou et al., 1998), respectively.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our ability to detect nonterminal endocytic events in BSC1 cells expressing Dab2 suggests the existence of some larger-than-normal CCPs or unresolvable clusters of CCPs, even in the presence of endogenous cargo levels.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Dab2 and CD8/LDLR expression can induce clathrin-coated structures (CCSs) that mimic nonterminal endocytic events
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results indicate that (i) Dab2 and ARH bind to the same cargo, (ii) both adaptors are recruited into the same CCSs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggested that factors recruited to AP2 complexes through interactions with their appendage domains might provide input into the endocytic checkpoint.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These effects suggest that additional factors, required to stabilize productive CCPs, become limiting during saturated CME.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that under these conditions, larger CCPs assemble so that a residual clathrin patch remains after CCV budding.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results demonstrate a strong CD8/LDLR-dependent membrane recruitment of both ARH and AP2 that, because CCP density does not change, results in a cargo-dependent increase of the adaptor protein content per CCP.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH stabilized AP2 at the plasma membrane
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and (iv) despite their partial functional redundancies and structural similarities, Dab2 and ARH exhibit fundamentally different, albeit cargo-dependent, interactions with CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations suggest that in the presence of low levels of cargo, clathrin and/or AP2 binding by Dab2 are required for its recruitment to CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Increased membrane recruitment of Dab2 is sufficient to induce GCCSs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In these cells, Dab2 mediates LDLR internalization, suggesting that these adaptors are partially redundant (Maurer and Cooper, 2006).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Introduction
What the sources say
- Not checked — no full text of the sourcecites Maurer and Cooper, 2006 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This recruitment of adaptor proteins had differential effects on CCP size and their dynamic behaviors.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“This idea is further supported by the observation that nonterminal events are more frequent in HeLa cells (Ehrlich et al., 2004; Merrifield et al., 2005; Loerke et al., 2009), which express relatively high levels of Dab2 and cargo (Maurer and Cooper, 2006; unpublished data).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
What the sources say
- Not checked yetcites Ehrlich et al., 2004 source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites Merrifield et al., 2005 source
- Not checked yetcites Loerke et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results indicate that (i) Dab2 and ARH bind to the same cargo”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Subsequently, we identified a subset of endocytic accessory factors, including membrane curvature and coat-sensing proteins, whose siRNA knockdown altered the rate and extent of turnover of abortive CCPs (Mettlen et al., 2009).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
What the sources say
- Not checked yetcites Mettlen et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data are consistent with the ability of CCPs to take up multiple distinct receptors.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In contrast to TfnR overexpression, which did not affect AP2 distribution (Loerke et al., 2009)”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
What the sources say
- Not checked yetcites Loerke et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results indicate that (i) Dab2 and ARH bind to the same cargo, (ii) both adaptors are recruited into the same CCSs, (iii) the size of CCPs can be controlled by the ratio of Dab2/ARH”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that variations in adaptor/cargo content can account, in part, for the dynamic heterogeneity of CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Previously, we showed that overexpression of TfnR, a constitutively internalized, AP2-dependent cargo, increased the efficiency of CCP maturation by increasing the contribution of productive CCPs at the expense of abortive species without affecting the rate of CCP maturation, i.e., the lifetimes of productive CCPs (Loerke et al., 2009).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion
What the sources say
- Not checked yetcites Loerke et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Not checked yet
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that ARH expression enhances CD8/LDLR uptake by increasing packaging, i.e., the number of CD8/LDLRs per CCP and/or the size of CCPs, rather than by enhancing either the efficiency or rate of CCP maturation.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“and its function is AP2 dependent (Maurer and Cooper, 2006).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Introduction
What the sources say
- Not checked — no full text of the sourcecites Maurer and Cooper, 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Together with our previous results (Loerke et al., 2009), we establish that even constitutively internalized cargo and their adaptors can regulate multiple aspects of CCP maturation”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
What the sources say
- Not checked yetcites Loerke et al., 2009 source
Checked before — its earlier verdict is held back until a new check runs.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Not checked yet
- It may state two separate claims as one. 45
- The quote only partly states this claim. 2
- Probably not a substantial claim. 5
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ARH can interact directly with both clathrin (He et al., 2002) and AP2 complexes (Mishra et al., 2005)”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
What the sources say
- Not matchedcites He et al., 2002
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Mishra et al., 2005 source
The Mishra et al. citation is attached to the AP-2 interaction, not the clathrin interaction. In Results and Discussion, the paper reports that an ARH-derived fusion binds AP-2 and identifies an independent AP-2-binding region. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Upon overexpression of CD8/LDLR, ARH-F259A exited the nucleus, but was not recruited into CCPs (Fig. 5 B).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > AP2 binding is required for CCP recruitment of ARH, whereas its nuclear export is passive and AP2 independent
What the sources say
- Partly supportedcites Mishra et al., 2005 sourceExperimental — accuracy not yet measured
The Results and Discussion report that F259A abolishes ARH binding to AP-2 and that GFP-tagged ARH fragments bearing F259A lose colocalization with AP-2. This supports the AP-2-binding aspect and is consistent with impaired recruitment to coated regions, but our copy does not report ARH-F259A exiting the nucleus upon CD8/LDLR overexpression or directly test its recruitment to CCPs under that condition. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of nonterminal events increased upon mild overexpression of cargo, and clusters of dynamic CCPs were observed.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this nucleo-cytoplasmic shuttling did not depend on AP2 binding and/or CCP recruitment, but on a functional PTB domain.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Upon CD8/LDLR expression, ARH exited the nucleus and was recruited to the plasma membrane, where it colocalized with clathrin (Fig. 4 C), and α-adaptin (Fig. 4 D) in diffraction-limited CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, unlike clathrin, but as for ARH-mCherry, these σ2-EGFP intensities began to decrease before LCa-EGFP.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“(iii) a mix of ARH and Dab2 led to the breakdown of GCCSs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“(iv) AP2 complexes are nonuniformly distributed in GCCSs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear? Based: unclearThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, ARH accumulation seemed to reach its maximum in CCPs with lifetimes >80 s, whereas clathrin intensities were higher in longer-lived cohorts.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“GCCS formation was dependent on Dab2 expression, as they were not detected in cells overexpressing CD8/LDLR alone (Fig. S2, E and F; see also Fig. 4, C and D).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When we coexpressed CD8/LDLR, Dab2-mCherry, and ARH-EGFP in BSC1 cells, both adaptors were recruited to the plasma membrane, where they colocalized (Fig. 4 E). However, in the presence of ARH, Dab2 and CD8/LDLR overexpression failed to generate GCCSs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“CD8/LDLR overexpression also increased signal intensities of all σ2-EGFP–labeled CCP cohorts (Fig. 8, E and F; red lines and bars, respectively) and prolonged the growth phase to ∼50 s.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, despite this dynamic behavior, CCVs were observed to pinch off from the edges of these GCCSs only on rare occasions, indicating that they are not endocytically active (Videos 4 and 5).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Dab2 and CD8/LDLR expression can induce clathrin-coated structures (CCSs) that mimic nonterminal endocytic events
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistent with this, ARH-containing CCPs almost always colocalized with AP2 (Fig. 4 D), even though we could readily detect clathrin-labeled CCPs that did not contain AP2 (Fig. S2 E, circles).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > AP2 binding is required for CCP recruitment of ARH, whereas its nuclear export is passive and AP2 independent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“productive CCPs, which ultimately lead to vesicle formation, contribute 50.7 ± 2.0% (mean ± jackknifed cell-to-cell error; Thomson and Chave, 1991) to the total number of CCPs found at the plasma membrane (Fig. 7 A), with early and late abortive CCPs representing 30.7 ± 1.3% and 17.0 ± 1.3%, respectively.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This activity was dependent on its abilities to bind LDLR through its PTB domain and to interact with AP2.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at the high levels of overexpression achieved upon complete removal of tet, Dab2 was strongly recruited to the plasma membrane and induced the formation of giant clathrin-coated structures (GCCSs).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increased efficiency of LDLR uptake upon ARH expression was not achieved through an increased CCP density, an increased percentage of productive CCPs, or an increased rate of their maturation.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The double mutant ARH-S117Y;F165A-mCherry was localized to the nucleus and failed to exit upon CD8/LDLR expression (Fig. 5 C), indicating a role for PTB binding interactions in the nuclear shuttling of ARH.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > AP2 binding is required for CCP recruitment of ARH, whereas its nuclear export is passive and AP2 independent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When TfnRs were overexpressed, even in the presence of Dab2 (Fig. S2 C), we did not detect an effect on CCP size or the appearance of GCCSs by immunofluorescence.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although biochemical measurements establish that CD8/LDLR endocytosis is saturable, resulting in a markedly decreased efficiency of CME”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“EM analysis of the ventral surface of cells revealed the appearance of larger flat lattices (Fig. 1 H), up to 500 nm in diameter (Table I), and clusters of CCPs (Fig. 1, F and H; see also Fig. 3 Ba) that were not detected under control conditions.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“EM revealed these to be flat lattices (Table I) and not clusters of CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unexpectedly, in cells overexpressing CD8/LDLR, Dab2-p67 induced the formation of GCCSs and colocalized with clathrin heavy chain (CHC; Fig. 2 C).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Increased membrane recruitment of Dab2 is sufficient to induce GCCSs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The calculated mean lifetimes were 5.7 ± 0.3 s, 19.1 ± 1.7 s, and 62.8 ± 3.1 s for early abortive, late abortive, and productive CCPs, respectively (Fig. 7 B).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An additional pool of ARH did not alter the lifetimes of productive CCPs (76.3 ± 5.2 s), despite increasing the efficiency of CD8/LDLR endocytosis (Fig. 6 B).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at the low levels of CD8/LDLR expression induced in the presence of 25 ng/ml tet (Fig. S1), CCPs increased in intensity (Fig. 1, E–G), suggesting an increase in CCP size and/or clustering of CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When CD8/LDLR and ARH were coexpressed, CCPs also grew in size, as detected by increased clathrin intensities and electron microscopy, yet they remained under the light-diffraction limit.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > CD8/LDLRs and their adaptors increase the size and dynamic behavior of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, although the relative intensities of these two markers could not be directly compared, an earlier decrease of the ARH-mCherry signals compared with LCa-EGFP signals (Fig. 8 D, arrows) led to a more symmetrical shape of the ARH-mCherry profiles.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“(ii) the competition of ARH and Dab2 for cargo binding, thereby disrupting Dab2 scaffolding of GCCSs”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also noted that stable ARH expression altered cell morphology such that the cells displayed a very broad and regular leading edge (Fig. 4 A, Fig. S3 A). These shape changes were accompanied by alterations in the actin cytoskeleton (Fig. S3, A and B), which were reversed upon CD8/LDLR expression, as ARH redistributed to CCPs (Fig. S3 C).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results demonstrate a continuum in the size of CCPs dependent on the expression levels of Dab2 and cargo: both Dab2 and CD8/LDLR overexpression are required for the formation of GCCSs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Relative amounts of Dab2 and CD8/LDLR control CCP size
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This apparent discrepancy reflects the fact that biochemical assays for ligand uptake measure CME indirectly and the efficiency of CME depends on cargo loading/concentration into CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > ARH is AP2 dependent and limiting during CD8/LDLR uptake
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The efficiency of CME depends on cargo loading/concentration into CCPs.
- Rests on an assumption: Biochemical assays for ligand uptake measure CME indirectly.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overexpression of a specific receptor and its adaptors alters the relative adaptor composition of CCPs and hence their dynamic behavior.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, although cargo overexpression is sufficient to trigger nuclear exit, AP2 interactions are required to stabilize ARH in CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > AP2 binding is required for CCP recruitment of ARH, whereas its nuclear export is passive and AP2 independent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This could potentially bypass the requirement for a threshold amount of AP2 and its associated partners, and hence disrupt signaling to the endocytic restriction/checkpoint.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although endocytosis of CD8/LDLRs was more efficient with increased amounts of ARH, the rescue was incomplete, indicating the existence of other rate-limiting components during uptake of high CD8/LDLR loads.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > ARH partially rescues saturated CME in an AP2-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, at higher cargo concentrations, other binding interactions, perhaps involving the remaining NPF motifs on Dab2-p67, are sufficient to stabilize Dab2 at the membrane, leading to the formation of larger CCPs and ultimately GCCSs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Increased membrane recruitment of Dab2 is sufficient to induce GCCSs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data indicate that CD8/LDLR overexpression stimulates initiation of CCPs, but does not affect the total number of productive CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Cargo overexpression prolongs the lifetime of productive CCPs
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these observations indicate that ARH interacts with and controls actin dynamics by an as yet unknown mechanism.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CCP localization of ARH is cargo dependent
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A similar dissociation/redistribution has been suggested for AP2 (Rappoport et al., 2005; Saffarian and Kirchhausen, 2008) and was further supported by our analysis of CCP cohorts labeled by σ2-EGFP.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
What the sources say
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which could account for the destabilization of nascent CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dab2 and ARH compete with each other and with AP2 for binding sites within the same CCPs as evidenced by (i) the strong colocalization of these various adaptors in CCPs, (ii) the competition of ARH and Dab2 for cargo binding, thereby disrupting Dab2 scaffolding of GCCSs, and (iii) the displacement of AP2 by ARH from cargo-laden CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ARH lacks a recognizable NLS, suggesting that an additional factor might be involved in its nuclear shuttling.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > AP2 binding is required for CCP recruitment of ARH, whereas its nuclear export is passive and AP2 independent
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Dab2-p96 binds to both clathrin and AP2, and localizes to CCPs, whereas Dab2-p67 lacks the main AP2- and clathrin-binding motifs and does not localize to CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > Increased membrane recruitment of Dab2 is sufficient to induce GCCSs
What the sources say
- Not matchedcites Xu et al., 1995
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“hence, the absence of ARH from CCPs under control conditions suggests that ARH recruitment is highly regulated and involves a yet-unidentified factor/mechanism.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Dab2 and ARH are differentially recruited to CCPs, yet compete for occupancy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the Dab2-dependent formation of nonfunctional, flat GCCSs under conditions of high cargo concentrations could reflect an imbalance of protein–protein interactions, possibly involving the disproportionate recruitment, through the multiple NPF motifs found in Dab2, of EH domain–containing proteins (e.g., Eps15, Eps15R, and intersectin) that bind directly or indirectly to clathrin.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Discussion > Adaptor content and the endocytosis checkpoint
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Rests on an assumption: Dab2 contains multiple NPF motifs that recruit EH domain-containing proteins that bind directly or indirectly to clathrin.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data establish that CD8/LDLR overexpression increases the size of CCPs, and ARH enhances this effect and increases the packaging efficiency of CD8/LDLR into these enlarged CCPs.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The apparently earlier disappearance of adaptors relative to clathrin indicates either their dissociation from CCPs before clathrin and/or a nonuniform redistribution of both ARH and AP2 in the clathrin lattice, resulting in their differential illumination within the TIRF field.”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Results > CD8/LDLRs increase the amount of coat components per CCP
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“there are conflicting reports as to whether LDLR and TfnR are internalized via the same or distinct CCPs (Keyel et al., 2006; Lakadamyali et al., 2006).”
§ Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis > Introduction
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The CD8/LDLR chimera is a valid model for LDLR endocytosis and its adaptor-dependent trafficking.
“The CD8/LDLR chimera comprises the extracellular and transmembrane domains of CD8 and the intracellular LDLR tail bearing a FXNPXY motif (Motley et al., 2003).”
The paper relies on this without support.
Fluorescent tags (mCherry, EGFP) do not alter the function of ARH, clathrin, or AP2.
“This expected localization of Dab2-mCherry suggests that the fluorescent tag did not interfere with its function.”
The paper relies on this without support.
Dab2 is recruited to CCPs and can function independently of AP2.
“Dab2, unlike ARH, is recruited to CCPs and can function independently of AP2.”
The paper relies on this without support.
The efficiency of CME depends on cargo loading/concentration into CCPs.
“the efficiency of CME depends on cargo loading/concentration into CCPs.”
The paper relies on this without support.
Biochemical assays for ligand uptake measure CME indirectly.
“biochemical assays for ligand uptake measure CME indirectly”
The paper relies on this without support.
Dab2 contains multiple NPF motifs that recruit EH domain-containing proteins that bind directly or indirectly to clathrin.
“through the multiple NPF motifs found in Dab2, of EH domain–containing proteins (e.g., Eps15, Eps15R, and intersectin) that bind directly or indirectly to clathrin.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Mean CCP area exceeds the stated maximum diameter at low CD8/LDLR expression
MajorThe text says these lattices reached at most 500 nm in diameter, but Table I gives a mean area of 0.45 μm2 for the same condition. Even a circular lattice 500 nm in diameter has an area of only about 0.196 μm2, so the reported mean cannot be below that maximum.
“EM analysis of the ventral surface of cells revealed the appearance of larger flat lattices (Fig. 1 H), up to 500 nm in diameter (Table I)”
“| CD8/LDLR | 25 | Dab2 | 0.45 ± 0.38a | 19 |”
Mean ARH-associated CCP area exceeds the stated maximum diameter
MajorThe stated maximum diameters are 500 nm for flat lattices and 165 nm for curved lattices, yet Table I reports a mean area of 0.89 μm2 for this condition. A 500-nm-diameter circle has an area of only about 0.196 μm2.
“EM analysis showed that the CCPs present in these cells consisted of flat and curved lattices, which remained below the diffraction limit (up to 500-nm and 165-nm diameter, respectively; Fig. S4 D, Table I).”
“| CD8/LDLR | 0 | ARH | 0.89 ± 0.54c | 27 |”
ARH localization is attributed to the wrong figure
MinorThe text cites Figure 3 A and B for nuclear ARH localization, whereas the Figure 4 caption identifies its A and B panels as the ARH-mCherry condition.
“the vast majority of ARH-mCherry was found in the nucleus of BSC1 cells (Fig. 3, A and B).”
“Figure: Figure 4. ARH localization is cargo dependent. BSC1 cells stably expressing ARH-mCherry were infected with adenoviruses coding for CD8/LDLR and cultured in the presence (A and B) or absence (C and D) of tet.”
Text cites a Figure 3 E panel absent from the caption
MinorThe text points to Figure 3 E for exchange kinetics, but the Figure 3 caption enumerates panels only through D.
“Dab2 and clathrin exchanged actively in these structures (Fig. 3 D), albeit with different kinetics (Fig. 3 E; Chetrit et al., 2009).”
“Figure: Figure 3. GCCSs are dynamic and, at moderate CD8/LDLR levels, generate nonterminal endocytic events. BSC1 cells were cultured as described in Fig. 1 and observed by dual-color TIRF-FM (A, Bb, C), electron microscopy (Ba), or spinning disk confocal microscopy (D).”
Citations
Cites
Robust single-particle tracking in live-cell time-lapse sequences
Jaqaman, K., Loerke, D., Mettlen, M., Kuwata, H., Grinstein, S., Schmid, S. L., & Danuser, G. M. (2008) · Nature Methods · doi:10.1038/nmeth.1237 · Cited by 1,974
Self-citationMolecular mechanism of the nuclear protein import cycle
Stewart, M. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2114 · Cited by 919
Endocytosis by random initiation and stabilization of clathrin-coated pits
Ehrlich, M., Boll, W., van Oijen, A., Hariharan, R., Chandran, K., Nibert, M. L., & Kirchhausen, T. (2004) · Cell · doi:10.1016/j.cell.2004.08.017 · Cited by 843
Signal-Dependent Membrane Protein Trafficking in the Endocytic Pathway
Trowbridge, I. S., Collawn, J. F., & Hopkins, C. R. (1993) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.09.110193.001021 · Cited by 811
Clathrin-mediated endocytosis in AP-2–depleted cells
Motley, A. M., Bright, N. A., Seaman, M. N. J., & Robinson, M. S. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200305145 · Cited by 709
Garcia, C. K., Wilund, K., Arca, M., Zuliani, G., Fellin, R., Maioli, M., Calandra, S., Bertolini, S., Cossu, F., Grishin, N., et al. (2001) · Science · doi:10.1126/science.1060458 · Cited by 624
Advances in spectrum analysis and array processing
Haykin, S. (1991) · Cited by 523
Lakadamyali, M., Rust, M. J., & Zhuang, X. (2006) · Cell · doi:10.1016/j.cell.2005.12.038 · Cited by 508
Merrifield, C. J., Perrais, D., & Zenisek, D. (2005) · Cell · doi:10.1016/j.cell.2005.03.015 · Cited by 476 · cited 4×
“…as sites at which multiple rounds of CCV formation were observed to occur from an apparently single CCP. Nonterminal events are frequently observed in HeLa cells (Merrifield et al., 2005; Loerke et al., 2009), but rarely detected in control BSC1 cells (Ehrlich et al., 2004; Loerke et al., 2009).”
BackgroundInfluentialCargo and dynamin regulate clathrin-coated pit maturation
Loerke, D., Mettlen, M., Yarar, D., Jaqaman, K., Jaqaman, H., Danuser, G., & Schmid, S. L. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000057 · Cited by 417
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Molecular mechanism and physiological functions of clathrin-mediated endocytosis
McMahon, H. T., & Boucrot, E. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3151 · Cited by 2,223
Mechanisms of clathrin-mediated endocytosis
Kaksonen, M., & Roux, A. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.132 · Cited by 1,698
A High Precision Survey of the Molecular Dynamics of Mammalian Clathrin-Mediated Endocytosis
Taylor, M. J., Perrais, D., & Merrifield, C. J. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000604 · Cited by 754
Weigel, A. V., Simon, B., Tamkun, M. M., & Krapf, D. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016325108 · Cited by 648
Regulation of Clathrin-Mediated Endocytosis
Mettlen, M., Chen, P.-H., Srinivasan, S., Danuser, G., & Schmid, S. L. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012644 · Cited by 614
Self-citation
Metadata
- Authors
- Mettlen, M., Loerke, D., Yarar, D., Danuser, G., & Schmid, S. L.
- Affiliations
- Scripps Research Institute (US)
- University of Denver (US)
- Corresponding author
- Schmid, Sandra L.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2010-03-15
- Volume
- 188
- Issue
- 6
- Pages
- 919-933
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2845073
- OpenAlex
- W2033344378
- Cited by
- 177
- References
- 42
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 13 · 2020: 12 · 2019: 10 · 2018: 10 · 2017: 10 · 2016: 11 · 2015: 14 · 2014: 10 · 2013: 13 · 2012: 17
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Leukemia and Lymphoma Society
- Thailand Science Research and Innovation
- National Institutes of Health (MH61345)
- National Institute of Mental Health (R01MH061345, MH61345, R37MH061345)
- National Institute of General Medical Sciences (R01GM073165)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- clathrin-mediated endocytosis, clathrin-coated pits, LDL receptor, Dab2, receptor internalization
- MeSH terms
- Animals, Cells, Cultured, Chlorocebus aethiops, Clathrin, Coated Pits, Cell-Membrane, Endocytosis, Ligands, Particle Size, Receptors, LDL, Time Factors, Adaptor Proteins, Signal Transducing, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
