The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index; 17 of the 34 sources its claims cite were checked for support.
The small GTPase RAB10 regulates endosomal recycling of the LDL receptor and transferrin receptor in hepatocytes
Open accessAbstract
The low-density lipoprotein receptor (LDLR) mediates the hepatic uptake of circulating low-density lipoproteins (LDLs), a process that modulates the development of atherosclerotic cardiovascular disease. We recently identified RAB10, encoding a small GTPase, as a positive regulator of LDL uptake in hepatocellular carcinoma cells (HuH7) in a genome-wide CRISPR screen, though the underlying molecular mechanism for this effect was unknown. We now report that RAB10 regulates hepatocyte LDL uptake by promoting the recycling of endocytosed LDLR from RAB11-positive endosomes to the plasma membrane. We also show that RAB10 similarly promotes the recycling of the transferrin receptor, which binds the transferrin protein that mediates the transport of iron in the blood, albeit from a distinct RAB4-positive compartment. Taken together, our findings suggest a model in which RAB10 regulates LDL and transferrin uptake by promoting both slow and rapid recycling routes for their respective receptor proteins.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
RAB10 promotes recycling of endocytosed LDLR and transferrin receptor (TFR) back to the plasma membrane in HuH7 hepatocytes. RAB10 depletion decreases LDL uptake but increases transferrin accumulation because LDL dissociates from LDLR while transferrin remains bound to TFR during recycling.
Key findings
- RAB10-targeted HuH7 cells showed decreased fluorescent LDL uptake and increased fluorescent transferrin accumulation versus nontargeting controls; wild-type and GTP-locked Q68L RAB10 rescued both phenotypes, whereas GDP-locked T23N did not (Fig. 1).
- RAB10 depletion increased total cellular LDLR and TFR protein by immunoblotting and flow cytometry, with unchanged mRNA levels, and reduced surface-displayed LDLR and TFR (Fig. 2).
- LDLR accumulated primarily in RAB11-positive recycling endosomes and TGN46-positive trans-Golgi network in RAB10-deleted cells, while TFR accumulated in RAB4-positive compartments; no significant changes were seen for EEA1, GM130, PDI, or LAMP1 in the relevant comparisons (Figs. 4–5).
- Endocytosis kinetics were unchanged for TFR–transferrin and LDLR–antibody assays, but TFR recycling was delayed: 50% of intracellular transferrin–TFR complexes recycled within 8 min in control cells versus 15–20 min in RAB10-targeted cells (Fig. 6).
Methods
- CRISPR-mediated RAB10 knockout in HuH7 cells, with lentiviral rescue using CRISPR-resistant wild-type, Q68L GTP-locked, or T23N GDP-locked RAB10 cDNA; clonal RAB10-deleted lines were also derived.
- Uptake, surface/total receptor flow cytometry, Western blotting, qRT-PCR, immunofluorescence confocal microscopy, and endocytosis/recycling assays using fluorescent LDL, fluorescent transferrin, or LDLR antibodies.
- Colocalization quantified by Mander’s and Pearson’s coefficients in Fiji/ImageJ; statistical tests included one-way ANOVA, two-way ANOVA, and Student’s t-test, with 2–4 biologic replicates and 10–30 cells per colocalization analysis.
Limitations
- Stated: germline deletion of RAB10 in mice causes embryonic lethality, limiting direct in vivo confirmation of the findings and suggesting that RAB10-mediated LDLR recycling as a therapeutic target may be limited by substantial off-target effects.
- Evident from the text: all experiments were performed in the HuH7 hepatocellular carcinoma cell line, with no in vivo or primary hepatocyte validation.
- Evident from the text: LDLR recycling was inferred largely from colocalization and surface/total receptor distribution, whereas direct recycling kinetics were measured for TFR but not for LDLR.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
17 of 34 cited sources checked · 5 supported · 3 flagged · accuracy not yet measured
- Findingown data
RAB10-targeted HuH7 cells exhibit increased accumulation of fluorescently labeled transferrin relative to control cells.
“RAB10-targeted cells exhibited decreased uptake of fluorescently labeled LDL and increased accumulation of fluorescently labeled transferrin relative to control cells treated with a nontargeting gRNA (Fig. 1B, C).”
- Also stated in: § Abstract · plain
“Deletion of RAB10 decreased cellular endocytosis of LDL but increased accumulation of another endocytic cargo, transferrin.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [13] Emmer, 2021, Genome-scale CRISPR screening for modifiers of cellular LDL uptake, PLoS Genet. source
The Results section on transferrin uptake reports that disrupting several genes decreased LDL uptake while enhancing transferrin uptake in HuH7 cells, but it does not identify RAB10 among them. Searches for RAB10 and RAB10-targeted cells found no passage establishing increased transferrin accumulation relative to controls. (LLM, conf=0.73)
Experimental — accuracy not yet measured
- Also stated in: § Abstract · plain
- Premisecitation
Transferrin remains in complex with TFR until it is released to the extracellular environment after TFR is recycled back to the plasma membrane.
“transferrin remains in complex with TFR until it is released to the extracellular environment after TFR is recycled back to the plasma membrane (18, 20).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [18] Ciechanover, 1983, Kinetics of internalization and recycling of transferrin and the transferrin receptor in a human hepatoma cell line. Effect of lysosomotropic agents, J. Biol. Chem. source
- cites [20] Mayle, 2012, The intracellular trafficking pathway of transferrin, Biochim. Biophys. Acta source
- Findingown data
RAB10-targeted HuH7 cells show increased immunofluorescence staining for TFR in punctae.
“immunofluorescence of RAB10-targeted cells revealed increased staining for both LDLR and TFR that remained distributed in punctae (Fig. 4).”
Quote in the paperSubstantial claim - Findingown data
RAB10 depletion causes intracellular accumulation of both LDLR and TFR in recycling organelles.
“Second, RAB10 depletion also caused an intracellular accumulation of both receptors in recycling organelles consistent with a delay in their plasma membrane recycling (Figs. 4H–I and 5G, H).”
Quote in the paperSubstantial claim - Findingown data
Heterologous expression of wild-type RAB10 cDNA rescues transferrin uptake in RAB10-targeted HuH7 cells.
“this heterologous expression of wild-type RAB10 cDNA rescued LDL and transferrin uptake, confirming that the observed effects of RAB10-targeting were mediated by on-target activity (Fig 1B, C).”
Quote in the paperSubstantial claim
- Findingown data
RAB10-targeted HuH7 cells show no change in LDLR transcript levels.
“with no corresponding change in LDLR transcript levels by qRT-PCR (Fig. 2D)”
Quote in the paperSubstantial claim - Findingown data
GTP-locked Q68L RAB10 shows decreased colocalization with Rab11 compared to wild-type RAB10.
“In comparison to wild-type RAB10, GTP-locked RAB10 demonstrated increased colocalization with TGN46 and decreased colocalization with Rab11 (Fig. 3F, G).”
Quote in the paperSubstantial claim - Findingown data
RAB10-targeted HuH7 cells show no change in TFR mRNA levels.
“while mRNA levels were unchanged (Fig. 2I)”
Quote in the paperSubstantial claim - Findingown data
GDP-locked T23N RAB10 has significantly decreased steady-state protein levels compared to wild-type RAB10.
“we observed significantly decreased steady-state protein levels for the GDP-locked mutant by both immunoblotting (Fig. 3D) and immunofluorescence (Fig. 3E).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Findingown data
There is no significant difference in the rate of endocytosis between RAB10-depleted and control cells for transferrin.
“with no significant difference in the rate of endocytosis between RAB10-depleted and control cells (Fig. 6B).”
Quote in the paperSubstantial claim - Findingown data
RAB10-targeted HuH7 cells exhibit decreased uptake of fluorescently labeled LDL relative to control cells.
“RAB10-targeted cells exhibited decreased uptake of fluorescently labeled LDL and increased accumulation of fluorescently labeled transferrin relative to control cells treated with a nontargeting gRNA (Fig. 1B, C).”
- Also stated in: § Abstract · plain
“Deletion of RAB10 decreased cellular endocytosis of LDL but increased accumulation of another endocytic cargo, transferrin.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Emmer, 2021, Genome-scale CRISPR screening for modifiers of cellular LDL uptake, PLoS Genet. source
Checked before — its earlier verdict is held back until a new check runs.
- Also stated in: § Abstract · plain
- Findingown data
In RAB10-deleted cells, intracellular accumulation of LDLR occurs primarily in RAB11-positive recycling endosomes.
“Colocalization analysis revealed the intracellular accumulation of LDLR to occur primarily in RAB11-positive recycling endosomes in RAB10-deleted cells (Fig. 4C, H)”
Quote in the paperSubstantial claim- Rests on an assumption: RAB11-positive endosomes are recycling endosomes.
- Findingown data
RAB10 deletion does not change LDLR colocalization with EEA1, RAB4, GM130, PDI, or Lamp1.
“with no change in colocalization with the early endosomal marker EEA1(Fig. 4A, H), the early endosomal/rapid recycling marker RAB4 (Fig. 4B, H), the cis-Golgi marker GM130(Fig. 4E, H), the ER marker PDI(Fig. 4F, H), or the lysosomal marker Lamp1(Fig. 4G, H).”
Quote in the paperSubstantial claim- Rests on an assumption: RAB4-positive compartments are rapid recycling compartments.
- Findingown data
Significant LDLR accumulation is observed in the trans-Golgi network in RAB10-deleted cells, as reflected by TGN46 colocalization.
“Significant LDLR accumulation was also observed in the trans-Golgi network, as reflected by TGN46 colocalization (Fig. 4D, H).”
Quote in the paperNot a substantial claim - Findingown data
RAB10-targeted HuH7 cells show reduced surface-displayed TFR protein levels.
“and surface-displayed protein levels were reduced (Fig. 2J)”
Quote in the paperSubstantial claim - Findingown data
Overexpression of wild-type or GTP-locked RAB10 increases the proportion of LDLR at the cell surface.
“overexpression of either wild-type or GTP-locked RAB10 had the opposite effect, increasing the proportion of LDLR at the cell surface (supplemental Fig S1B).”
Quote in the paperSubstantial claim - Findingown data
There is no difference in the rate of LDLR endocytosis between control and RAB10-depleted cells.
“Similar to TFR, no difference was observed in the rate of LDLR endocytosis between control and RAB10-depleted cells (Fig. 6D).”
Quote in the paperSubstantial claim - Findingown data
RAB10-targeted HuH7 cells show increased immunofluorescence staining for LDLR in punctae.
“immunofluorescence of RAB10-targeted cells revealed increased staining for both LDLR and TFR that remained distributed in punctae (Fig. 4).”
Quote in the paperSubstantial claim - Findingown data
RAB10 deletion alters LDLR intracellular distribution.
“Fig. 4 RAB10 deletion alters LDLR intracellular distribution.”
Quote in the paperSubstantial claim - Findingown data
RAB10-targeting results in a significant delay in TFR recycling.
“RAB10-targeting resulted in a significant delay in TFR recycling, with 50% of the intracellular transferrin–TFR complexes recycled within 8 min for control cells compared to 15–20 min for RAB10-targeted cells (Fig. 6E).”
Quote in the paperSubstantial claim - Findingown data
GTP-locked Q68L RAB10 shows increased colocalization with TGN46 compared to wild-type RAB10.
“In comparison to wild-type RAB10, GTP-locked RAB10 demonstrated increased colocalization with TGN46 and decreased colocalization with Rab11 (Fig. 3F, G).”
Quote in the paperNot a substantial claim - Findingown data
In RAB10-targeted cells, TFR colocalization with RAB4 is significantly increased.
“A similar analysis of TFR redistribution in RAB10-targeted cells revealed a significant increase in colocalization with RAB4 (Fig. 5B, G)”
Quote in the paperSubstantial claim - Findingown data
RAB10-targeted HuH7 cells exhibit increased total cellular LDLR protein levels.
“these same cells exhibited increased levels of total cellular LDLR protein, as measured by both immunoblotting (Fig. 2A, B) and by flow cytometry of permeabilized cells (Fig. 2C)”
Quote in the paperSubstantial claim - Findingown data
Heterologous expression of wild-type RAB10 cDNA rescues LDL uptake in RAB10-targeted HuH7 cells.
“this heterologous expression of wild-type RAB10 cDNA rescued LDL and transferrin uptake, confirming that the observed effects of RAB10-targeting were mediated by on-target activity (Fig 1B, C).”
Quote in the paperSubstantial claim - Findingown data
Internalization of surface-bound fluorescent transferrin is complete within 5-10 min.
“For the fluorescent transferrin that was bound to the cell surface, internalization was complete within 5–10 min”
Quote in the paperSubstantial claim - Findingown data
At time zero, less fluorescent transferrin is bound to RAB10-depleted cells compared to control cells.
“At time zero, less fluorescent transferrin was bound to RAB10-depleted cells compared to control cells (Fig. 6A)”
Quote in the paperNot a substantial claim - Findingown data
In RAB10-targeted cells, TFR colocalization with EEA1 is reduced.
“and a reduced colocalization with EEA1 (Fig. 5A, G).”
Quote in the paperSubstantial claim - Findingown data
RAB10 deletion alters intracellular distribution of TFR.
“Fig. 5 RAB10 deletion alters intracellular distribution of TFR.”
Quote in the paperSubstantial claim - Findingown data
RAB10-targeted HuH7 cells show redistribution of cellular LDLR protein from the cell surface to intracellular compartments.
“flow cytometry of nonpermeabilized RAB10-targeted cells demonstrated a redistribution of cellular LDLR protein from the cell surface to intracellular compartments (Figs. 2E and S1A)”
Quote in the paperSubstantial claim - Findingown data
Steady-state levels of GTP-locked Q68L RAB10 are comparable to wild-type RAB10.
“steady-state levels of the GTP-locked (Q68L) mutant were comparable to those of wild-type RAB10 (Fig 3D, E).”
Quote in the paperNot a substantial claim - Findingown data
In RAB10-targeted cells, there is no significant increase in TFR colocalization with Rab11 and TGN46.
“In contrast to LDLR, no significant increase in colocalization was observed for TFR with Rab11 and TGN46 (Fig. 5C, D, G).”
Quote in the paperSubstantial claim - Findingown data
RAB10-targeted HuH7 cells exhibit increased total cellular TFR protein levels.
“the effect on TFR abundance mirrored its effect on LDLR, with total cellular TFR protein levels increased (Fig. 2F–H)”
Quote in the paperSubstantial claim - Findingreasoning
The association of GTP-locked RAB10 mutant with recycling endosomes is decreased.
“Fourth, the association of GTP-locked RAB10 mutant with recycling endosomes was decreased”
Quote in the paperSubstantial claim - Findingown data
In RAB10-targeted cells, there is no change in TFR colocalization with markers of the cis-Golgi network or the ER.
“Similar to LDLR, no change in TFR colocalization was observed for markers of the cis-Golgi network (Fig. 5E, G) or the ER (Fig. 5F, G).”
Quote in the paperNot a substantial claim - Findingreasoning
Less fluorescent antibody is bound at time zero in RAB10-depleted cells compared to control cells for LDLR.
“Consistent with decreased surface LDLR in RAB10-depleted cells, less fluorescent antibody was bound at time zero compared to control cells (Figs. 6C and 2E).”
Quote in the paperNot a substantial claim - Findingown data
Kinetic experiments confirmed a delay in TFR recycling to the plasma membrane.
“Finally, kinetic experiments confirmed a delay in TFR recycling to the plasma membrane (Fig. 6D).”
Quote in the paperSubstantial claim - Premisecitation
RAB10 is a positive regulator of LDL uptake in HuH7 cells in a genome-wide CRISPR screen.
“This screen identified RAB10, a small GTPase known to mediate trafficking of vesicles between intracellular compartments, as a key regulator of LDL uptake.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Emmer, 2021, Genome-scale CRISPR screening for modifiers of cellular LDL uptake, PLoS Genet. source
Checked before — its earlier verdict is held back until a new check runs.
- Interpretationown data
RAB10 promotes the recycling of TFR.
“RAB10 promotes the recycling of TFR”
Quote in the paperSubstantial claim - Study design and conductown data
The observed effects of RAB10-targeting on LDL and transferrin uptake were mediated by on-target activity.
“confirming that the observed effects of RAB10-targeting were mediated by on-target activity (Fig 1B, C).”
Quote in the paperSubstantial claim - Interpretationreasoning
The discrepancy between ligand and receptor effects is likely due to different fates of the two ligands following uptake: LDL dissociates from LDLR while transferrin remains in complex with TFR during recycling until its release extracellularly.
“This discrepancy was likely due to the different fates of the two ligands following uptake, with LDL undergoing dissociation from LDLR while transferrin remains in complex with TFR during recycling until its release extracellularly.”
Quote in the paperSubstantial claim- Rests on an assumption: Transferrin remains in complex with TFR during recycling until its release extracellularly.
- Interpretationown data
The active form of RAB10 accelerates anterograde transport of cargo vesicles out of the recycling endosome compartment.
“consistent with this active form accelerating the anterograde transport of cargo vesicles out of this compartment.”
Quote in the paperSubstantial claim - Interpretationown data
RAB10 depletion affects distribution of LDLR and TFR in distinct recycling compartments.
“These findings suggest that RAB10 depletion affects distribution of LDLR and TFR in distinct recycling compartments.”
Quote in the paperSubstantial claim - Interpretationreasoning
The discordant effects of RAB10 targeting on LDL and transferrin cellular accumulation are a result of different fates of the labeled ligand rather than their corresponding receptors.
“These similarities suggest that the discordant effects of RAB10 targeting on LDL and transferrin cellular accumulation are a result of different fates of the labeled ligand rather than their corresponding receptors.”
Quote in the paperSubstantial claim - Interpretationreasoning
RAB10 has potential to directly regulate vesicular trafficking of LDLR and TFR.
“Together, these findings highlight the heterogeneous subcellular distribution of RAB10, its modulation by the GTPase cycle, and its potential to directly regulate the vesicular trafficking of LDLR and TFR.”
Quote in the paperSubstantial claim- Rests on an assumption: HuH7 cells are a valid model for hepatocyte LDLR and TFR trafficking.
- Interpretationown data
RAB10 regulates hepatocyte LDL uptake by promoting the recycling of endocytosed LDLR from RAB11-positive endosomes to the plasma membrane.
“We now report that RAB10 regulates hepatocyte LDL uptake by promoting the recycling of endocytosed LDLR from RAB11-positive endosomes to the plasma membrane.”
Quote in the paperSubstantial claim- Rests on an assumption: HuH7 cells are a valid model for hepatocyte LDLR and TFR trafficking.
- Rests on an assumption: RAB11-positive endosomes are recycling endosomes.
- Interpretationown data
RAB10 promotes the recycling of the transferrin receptor from a distinct RAB4-positive compartment.
“We also show that RAB10 similarly promotes the recycling of the transferrin receptor, which binds the transferrin protein that mediates the transport of iron in the blood, albeit from a distinct RAB4-positive compartment.”
Quote in the paperSubstantial claim- Rests on an assumption: HuH7 cells are a valid model for hepatocyte LDLR and TFR trafficking.
- Rests on an assumption: RAB4-positive compartments are rapid recycling compartments.
- Premisecitation
Internalized LDL is released from LDLR in acidic compartments.
“internalized LDL is released from LDLR in acidic compartments (29, 30)”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Germline deletion of RAB10 in mice results in embryonic lethality.
“In further support of the breadth of cellular functions for RAB10, germline deletion of RAB10 in mice results in embryonic lethality (53).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [53] Lv, 2015, Targeted disruption of Rab10 causes early embryonic lethality, Protein Cell source
Checked before — its earlier verdict is held back until a new check runs.
- Interpretationreasoning
RAB10, the exocyst, and STX4 may work together to coordinate the trafficking, tethering, and fusion of LDLR and TFR-containing recycling vesicles, similar to their role in GLUT4 vesicular trafficking.
“Taken together, these findings suggest that RAB10, the exocyst, and STX4 may work together to coordinate the trafficking, tethering, and fusion of LDLR and TFR-containing recycling vesicles, similar to their role in GLUT4 vesicular trafficking.”
Quote in the paperSubstantial claim - Interpretationreasoning
RAB10 may promote the recycling of LDLR and TFR through the recruitment of the exocyst to recycling vesicles.
“Taken together, these findings suggest that RAB10 may promote the recycling of LDLR and TFR through the recruitment of the exocyst to recycling vesicles.”
Quote in the paperSubstantial claim - Interpretationown data
RAB10 deletion has differential effects on LDLR and TFR recycling.
“Fig. 7 Differential effects of RAB10 deletion on LDLR and TFR recycling.”
Quote in the paperSubstantial claim - Interpretationcitation
The embryonic lethality of RAB10 germline deletion limits direct confirmation of our current findings in an in vivo mouse model.
“This latter observation limits the direct confirmation of our current findings in an in vivo mouse model”
Quote in the paperSubstantial claim - Interpretationreasoning
The potential for RAB10-mediated LDLR recycling as a therapeutic target is likely to be limited by substantial off-target effects.
“suggests that the potential for RAB10-mediated LDLR recycling as a therapeutic target is likely to be limited by substantial off-target effects.”
Quote in the paperSubstantial claim
- Probably not a substantial claim. 13
- It may state two separate claims as one. 23
- The quote only partly states this claim. 1
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationIDOL is a ubiquitin ligase that induces proteasomal degradation of LDLR.
“IDOL, a ubiquitin ligase that induces proteasomal degradation of LDLR (11, 12).”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [11] Zhang, 2016, IDOL, inducible degrader of low-density lipoprotein receptor, serves as a potential therapeutic target for dyslipidemia, Med. Hypotheses source
- cites [12] Zhang, 2011, The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor, Genes Dev. source
The section “UBE2D family proteins are the E2 enzymes for LDLR ubiquitination” identifies IDOL as the ligase involved in LDLR degradation, but contradicts the claimed pathway: IDOL-dependent LDLR degradation was blocked by the lysosomal inhibitor bafilomycin, not the proteasomal inhibitor MG-132. MG-132 stabilized IDOL itself, not LDLR. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationPrevious studies have revealed heterogeneity in recycling of different receptors: LDLR is transported along a RAB11-mediated slow recycling pathway involving the endocytic recycling compartment, while TFR utilizes both RAB11- and RAB4-mediated rapid recycling pathways.
“Previous studies have revealed heterogeneity in the recycling of different receptors, with some, including LDLR, transported along a RAB11-mediated slow recycling pathway involving the endocytic recycling compartment, while others, including TFR, utilize both RAB11- and RAB4-mediated rapid recycling pathways (20, 42, 43).”
Quote in the paperSubstantial claim3 of 3 sources checked- cites [20] Mayle, 2012, The intracellular trafficking pathway of transferrin, Biochim. Biophys. Acta source
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured - cites [42] Mayor, 1993, Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process, J. Cell Biol. source
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured - cites [43] Sheff, 1999, The receptor recycling pathway contains two distinct populations of early endosomes with different sorting functions, J. Cell Biol. source
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationThe receptors for LDL (LDLR) and transferrin receptor (TFR) are both endocytosed from the cell surface via clathrin-coated vesicles and transported through intracellular recycling pathways.
“The receptors for LDL (LDLR) and transferrin receptor (TFR) are both endocytosed from the cell surface via clathrin-coated vesicles and transported through intracellular recycling pathways (14, 15, 16, 17, 18, 19, 20).”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [14] Goldstein, 2015, A century of cholesterol and coronaries: from plaques to genes to statins, Cell source
In “LDL Receptor Pathway Elucidated” (page unavailable), the paper says LDL receptors cluster in coated pits for endocytosis. “PCSK9: A Protein that Destroys LDL Receptors and Raises LDL” (page unavailable) describes a mechanism that returns internalized LDL receptors to the cell surface. Our copy does not address transferrin receptors, so it does not support the claim that both receptors follow these pathways. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [15] Pietiäinen, 2013, NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation, J. Cell Sci. source
- cites [16] Brown, 1979, Receptor-mediated endocytosis: insights from the lipoprotein receptor system, Proc. Natl. Acad. Sci. U. S. A. source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationThe previously reported CRISPR screen for modifiers of LDL uptake identified RABIF, a guanine nucleotide exchange factor that stimulates GDP release from various Rab GTPases including RAB10, and which has also been shown to stabilize RAB10.
“The previously reported CRISPR screen for modifiers of LDL uptake (13) also identified RABIF (Rab interacting factor), a guanine nucleotide exchange factor that stimulates GDP release from various Rab GTPases including RAB10, and which has also been shown to stabilize RAB10 (46).”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [13] Emmer, 2021, Genome-scale CRISPR screening for modifiers of cellular LDL uptake, PLoS Genet. source
The Results sections describe the CRISPR screen and its LDL-uptake hits, but searches for “RABIF” and “Rab interacting factor” found no passage identifying RABIF as a hit in our copy. The sentence cites this paper for that identification; it separately cites reference 46 for RABIF’s activity and RAB10 stabilization. (LLM, conf=0.72)
Experimental — accuracy not yet measured - cites [46] Gulbranson, 2017, RABIF/MSS4 is a Rab-stabilizing holdase chaperone required for GLUT4 exocytosis, Proc. Natl. Acad. Sci. U. S. A. source
The Results report that RABIF stimulates GDP release from Rab10 in vitro, and the Significance section says it stabilizes Rab10. However, the paper calls RABIF a putative GEF and concludes that it does not function as a GEF in GLUT4 exocytosis. The LDL-uptake screen is cited separately as reference 13, not attributed to this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationAssociation of RAB10 with the exocyst complex has been reported in renal epithelial cells.
“Association of RAB10 with the exocyst complex has also been reported in renal epithelial cells (45).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [45] Babbey, 2010, Rab10 associates with primary cilia and the exocyst complex in renal epithelial cells, Am. J. Physiol. Ren. Physiol. source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationGTP-bound RAB10 mediates insulin-stimulated transport of GLUT4-containing vesicles to the plasma membrane via recruitment of the exocyst membrane tethering complex.
“Intriguingly, GTP-bound RAB10 has previously been demonstrated to mediate the insulin-stimulated transport of GLUT4-containing vesicles to the plasma membrane via its recruitment of the exocyst membrane tethering complex (44).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [44] Sano, 2015, A potential link between insulin signaling and GLUT4 translocation: association of Rab10-GTP with the exocyst subunit Exoc6/6b, Biochem. Biophys. Res. Commun. source
The Introduction reports that Rab10-GTP binds the exocyst subunits Exoc6/6b and that these subunits participate in GLUT4 translocation in adipocytes. The Discussion calls this interaction a proposed link to vesicle exocytosis and says how the exocyst interacts with GLUT4 vesicles in response to insulin remains to be determined. Thus, the paper does not demonstrate the claimed recruitment mechanism for transport to the plasma membrane. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationRAB10 has been implicated in diverse areas of membrane trafficking in different cell types, including formation of noncanonical macropinosome tubules in macrophages, vesicle transportation from early endosome to recycling endosome in C. elegans, and Golgi to plasma membrane transport in macrophages.
“RAB10 has also been implicated in diverse areas of membrane trafficking in different cell types, including formation of noncanonical macropinosome tubules in macrophages (49), vesicle transportation from early endosome to recycling endosome in C. elegans (31), and Golgi to plasma membrane transport in macrophages (32).”
Quote in the paperNot a substantial claim3 of 3 sources checked- cites [49] Kawai, 2021, Rab10-positive tubular structures represent a novel endocytic pathway that diverges from canonical macropinocytosis in RAW264 macrophages, Front. Immunol. source
- cites [31] Chen, 2006, RAB-10 is required for endocytic recycling in the Caenorhabditis elegans intestine, Mol. Biol. Cell source
- cites [32] Wang, 2010, Ras-related protein Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane, Proc. Natl. Acad. Sci. U. S. A. source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationRAB10 has been localized to multiple subcellular compartments in different cell types including the endoplasmic reticulum, trans Golgi network, early endosomes, recycling endosomes, phagosomes, and primary cilia.
“Consistent with this wide range of functions, RAB10 has been localized to multiple subcellular compartments in different cell types including the endoplasmic reticulum, trans Golgi network, early endosomes, recycling endosomes, phagosomes, and primary cilia (25, 31, 32, 50, 51, 52).”
Quote in the paperNot a substantial claim3 of 3 sources checked- cites [25] English, 2013, Rab10 GTPase regulates ER dynamics and morphology, Nat. Cell Biol. source
In Results, ‘Rab10 localizes to the ER’ (page not provided), the paper reports Rab10 at the ER and Golgi, but does not specify the trans-Golgi network. It reports no localization to early or recycling endosomes in the Cos-7 cells tested, and does not address phagosomes or primary cilia. Because the claim spans different cell types, the Cos-7 result does not rule out localization elsewhere. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [31] Chen, 2006, RAB-10 is required for endocytic recycling in the Caenorhabditis elegans intestine, Mol. Biol. Cell source
The Results (page unavailable) place RAB-10 on a subset of early endosomes and describe its association with the TGN and/or apical recycling endosomes in C. elegans intestinal cells. The paper does not establish the claimed localization to the endoplasmic reticulum, phagosomes, or primary cilia. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [32] Wang, 2010, Ras-related protein Rab10 facilitates TLR4 signaling by promoting replenishment of TLR4 onto the plasma membrane, Proc. Natl. Acad. Sci. U. S. A. source
The Results and Discussion section reports Rab10 localization in Golgi and early endosomal compartments in RAW264.7 cells, supporting the trans-Golgi-network and early-endosome portions of the claim. It does not establish localization in the endoplasmic reticulum, recycling endosomes, phagosomes, or primary cilia, or document the claimed range across different cell types. (LLM, conf=0.86)
Experimental — accuracy not yet measured
It may state two separate claims as one.
FindingreasoningRAB10 depletion has similar effects on LDLR and TFR despite opposing effects on LDL and transferrin uptake.
“Unexpectedly, in contrast to the opposing effects of RAB10 depletion on LDL and transferrin uptake, we observed similar effects on their corresponding receptors, LDLR and TFR.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIn RAB10-targeted HuH7 cells, expression of wild-type or GTP-locked Q68L RAB10 rescues transferrin uptake, whereas GDP-locked T23N RAB10 does not.
“Expression of both wild-type and GTP-locked RAB10 (Q68L) rescued the LDL (Fig. 1B) and transferrin (Fig. 1C) uptake phenotype of RAB10-targeted cells, whereas expression of GDP-locked RAB10 (T23N) had no effect.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIn the current report, RAB10 depletion decreases LDL cellular accumulation and increases transferrin cellular accumulation.
“In the current report, we confirmed the discordant effects of RAB10 on LDL and transferrin cellular accumulation, with the former decreased and the latter increased upon RAB10 depletion (Fig. 1B, C).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataA subpopulation of RAB10 colocalizes with both LDLR and TFR and with recycling endosomes.
“Third, a subpopulation of RAB10 was found to colocalize with both receptors and with recycling endosomes.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataRAB10 colocalizes with markers of the early endosome (EEA1), recycling endosome (RAB11), trans-Golgi network (TGN46), and endoplasmic reticulum (ER, PDI) in HuH7 cells.
“We observed colocalization of RAB10 with markers of the early endosome (EEA1), recycling endosome (RAB11), trans-Golgi network (TGN46), and endoplasmic reticulum (ER, PDI) (Fig. 3B)”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataA large pool of RAB10 colocalizes with RAB11-positive recycling endosomes and PDI-positive ER in HuH7 cells.
“We also observed a large pool of RAB10 colocalized with RAB11-positive recycling endosomes and with the PDI-positive ER (Fig. 3C).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataRAB10 depletion causes a decrease in the amount of both LDLR and TFR on the cell surface without a corresponding decrease in gene expression.
“First, RAB10 depletion caused a decrease in the amount of both receptors on the cell surface without a corresponding decrease in gene expression (Fig. 2).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIn RAB10-targeted HuH7 cells, expression of wild-type or GTP-locked Q68L RAB10 rescues LDL uptake, whereas GDP-locked T23N RAB10 does not.
“Expression of both wild-type and GTP-locked RAB10 (Q68L) rescued the LDL (Fig. 1B) and transferrin (Fig. 1C) uptake phenotype of RAB10-targeted cells, whereas expression of GDP-locked RAB10 (T23N) had no effect.”
Quote in the paperSubstantial claimIt may state two separate claims as one. The quote only partly states this claim.
Findingown dataRAB10 does not alter the kinetics of endocytosis for LDLR or TFR.
“RAB10 does not alter the kinetics of endocytosis for LDLR or TFR”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataUpon RAB10 depletion, LDLR accumulates in RAB11-positive punctae and TFR accumulates in RAB4-positive punctae.
“as we observed LDLR accumulation in RAB11-positive punctae and TFR accumulation in RAB4-positive punctae upon RAB10 depletion.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataWe observed significant subpopulations of RAB10 in several subcellular compartments.
“We also observed significant subpopulations of RAB10 in several subcellular compartments.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Interpretationown dataRAB10 promotes the recycling of both LDLR and TFR.
“Several lines of evidence support a model in which RAB10 promotes the recycling of both LDLR and TFR.”
- Also stated in: § Discussion · boosted
“together with our demonstration that multiple receptors depend on RAB10 for recycling”
Quote in the paperSubstantial claim- Also stated in: § Discussion · boosted
It may state two separate claims as one.
InterpretationreasoningRAB10 regulates LDL and transferrin uptake by promoting both slow and rapid recycling routes for their respective receptor proteins.
“Taken together, our findings suggest a model in which RAB10 regulates LDL and transferrin uptake by promoting both slow and rapid recycling routes for their respective receptor proteins.”
Quote in the paperSubstantial claim- Rests on an assumption: HuH7 cells are a valid model for hepatocyte LDLR and TFR trafficking.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationThe acidic environment of the endosomal lumen induces complex dissociation, with LDL transported to the lysosome for hydrolysis, and free LDLR recycled back to the plasma membrane.
“The acidic environment of the endosomal lumen induces complex dissociation, with LDL subsequently transported to the lysosome for hydrolysis, and free LDLR recycled back to the plasma membrane (8, 9).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationPCSK9 is a negative regulator that redirects LDLR to the lysosome for degradation.
“PCSK9, a negative regulator that redirects LDLR to the lysosome for degradation (10)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] Horton, 2007, Molecular biology of PCSK9: its role in LDL metabolism, Trends Biochem. Sci. source
It may state two separate claims as one.
InterpretationreasoningIn RAB10-deleted cells, only transferrin, which remains in complex with TFR, accumulates, while LDL does not because LDL dissociates from LDLR and undergoes degradation within lysosomes.
“Despite both LDLR and TFR accumulating within recycling compartments, only transferrin, which remains in complex with TFR, also accumulates in RAB10-deleted cells, as LDL dissociates from LDLR and undergoes degradation within lysosomes.”
Quote in the paperSubstantial claim- Rests on an assumption: Transferrin remains in complex with TFR during recycling until its release extracellularly.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationA recent study based on published proteomic data and CRISPR/Cas9 screens identified a correlation between RAB10 and STX4.
“A recent study based on published proteomic data and CRISPR/Cas9 screens also identified a correlation between RAB10 and STX4 (48).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48] Clague, 2020, Data mining for traffic information, Traffic source
Checked before — its earlier verdict is held back until a new check runs.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationThe same screen identified STX4, a SNARE protein that facilitates docking and fusion of transport vesicles with the cell membrane and has been implicated in fusion of GLUT4 vesicles with the plasma membrane.
“This screen also identified STX4, a SNARE protein that facilitates docking and fusion of transport vesicle with the cell membrane and has been similarly implicated in the fusion of GLUT4 vesicles with the plasma membrane (47).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] Leto, 2012, Regulation of glucose transport by insulin: traffic control of GLUT4, Nat. Rev. Mol. Cell Biol. source
It may state two separate claims as one.
Interpretationown dataRAB10 is involved in both the slow (RAB11-mediated) and rapid (RAB4-mediated) recycling pathways.
“Our results implicate RAB10 in both pathways”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Interpretationown dataRAB10 regulates recycling but not endocytosis.
“Fig. 6 RAB10 regulates recycling but not endocytosis.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationOur prior screen of LDL uptake modifiers identified several exocyst components (EXOC1, EXOC2, EXOC3, EXOC4, EXOC7, EXOC8) that phenocopied RAB10, with depletion of either protein resulting in decreased LDL uptake and increased transferrin accumulation.
“Our prior screen of LDL uptake modifiers likewise identified several exocyst components including EXOC1, EXOC2, EXOC3, EXOC4, EXOC7, and EXOC8 that phenocopied RAB10, with depletion of either protein resulting in decreased LDL uptake and increased transferrin accumulation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Emmer, 2021, Genome-scale CRISPR screening for modifiers of cellular LDL uptake, PLoS Genet. source
Checked before — its earlier verdict is held back until a new check runs.
It may state two separate claims as one.
Interpretationown dataRAB10 deletion results in a defect in trafficking of both fast and slow recycling vesicles, leading to accumulation of LDLR in RAB11-positive ERC and TFR in RAB4-positive fast recycling vesicles, resulting in reduced cell surface LDLR and TFR.
“Deletion of RAB10 results in a defect in trafficking of both fast and slow recycling vesicles, leading to accumulation of LDLR in RAB11-positive ERC and TFR in RAB4-positive fast recycling vesicles, resulting in reduced cell surface LDLR and TFR.”
Quote in the paperSubstantial claim
The paper relies on this without support.
HuH7 cells are a valid model for hepatocyte LDLR and TFR trafficking.
“We now report that RAB10 regulates hepatocyte LDL uptake by promoting the recycling of endocytosed LDLR from RAB11-positive endosomes to the plasma membrane.”
The paper relies on this without support.
RAB10 mediates trafficking of vesicles between intracellular compartments.
“This screen identified RAB10, a small GTPase known to mediate trafficking of vesicles between intracellular compartments, as a key regulator of LDL uptake.”
The paper relies on this without support.
RAB11-positive endosomes are recycling endosomes.
“We observed colocalization of RAB10 with markers of the early endosome (EEA1), recycling endosome (RAB11), trans-Golgi network (TGN46), and endoplasmic reticulum (ER, PDI) (Fig. 3B)”
The paper relies on this without support.
RAB4-positive compartments are rapid recycling compartments.
“with no change in colocalization with the early endosomal marker EEA1(Fig. 4A, H), the early endosomal/rapid recycling marker RAB4 (Fig. 4B, H), the cis-Golgi marker GM130(Fig. 4E, H), the ER marker PDI(Fig. 4F, H), or the lysosomal marker Lamp1(Fig. 4G, H).”
The paper relies on this without support.
Fluorescently labeled LDL and transferrin trace the same endocytic and recycling pathways as their unlabeled ligands.
“For uptake assays, cells were washed with serum-free DMEM and then incubated in DMEM containing either 4 μg/ml DyLight550-conjugated LDL (Cayman Chemical) or 5 μg/ml Alexa Fluor 555-conjugated transferrin (ThermoFisher Scientific) at 37°C for 1 h or 30 min, respectively.”
The paper relies on this without support.
Transferrin remains in complex with TFR during recycling until its release extracellularly.
“with LDL undergoing dissociation from LDLR while transferrin remains in complex with TFR during recycling until its release extracellularly.”
The paper relies on this without support.
The majority (80%–90%) of apo transferrin bound TFR is recycled through a fast-recycling route to the cell surface.
“The majority (80%–90%) of apo transferrin bound TFR is recycled through a fast-recycling route to the cell surface.”
The paper relies on this without support.
LDLR is transported via an endocytic recycling compartment (ERC) and recycled to the cell surface.
“LDLR is then transported via an endocytic recycling compartment (ERC) and recycled to the cell surface.”
The paper relies on this without support.
LDL-bound LDLR and holo transferrin–bound TFR undergo clathrin-mediated endocytosis, upon which LDLR releases LDL and transferrin releases iron molecules within sorting endosome.
“LDL-bound LDLR and holo transferrin–bound TFR undergo clathrin-mediated endocytosis, upon which LDLR releases LDL and transferrin releases iron molecules within sorting endosome.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The prior CRISPR screen detected novel regulators of LDL uptake that were reproducible across independent replicates and during follow-up testing.
“We also detected novel regulators of LDL uptake that were reproducible across independent replicates and during follow up testing56,57.”
From Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening (2025) · cites this paper as [57]
The Abstract and Discussion report that a prior CRISPR screen identified RAB10 and other modifiers of LDL uptake. The Results section, “RAB10 regulates the cellular uptake of LDL and transferrin,” reports follow-up experiments confirming RAB10’s effect, with independent biological replicates shown in Fig. 1. Our copy does not establish that the screen’s novel regulators generally were reproducible across independent screen replicates and follow-up tests. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe study extended the known Retromer regulators to include DENND4A and DENND4C, TBC1D13, and a TBC1D1/TBC1D4 heterodimer, establishing mechanistic links between Retromer and the switching of RAB10 and RAB35.
“We have now extended these regulators to include DENND4A and DENND4C, TBC1D13, and a TBC1D1/TBC1D4 heterodimer, and in so doing, established mechanistic links between Retromer and the switching of RAB10 and RAB35; two RAB GTPases previously linked to the regulation of endosomal cargo recycling85,88–90,92,96,101,121,122.”
From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [92]
Activation of RAB10 is heavily implicated in general endosomal cargo recycling.
“Activation of RAB10 is heavily implicated in general endosomal cargo recycling85–93”
From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [92]
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.
TFR recycling result cites the endocytosis panel
MinorThe discussion cites Fig. 6D as evidence of delayed TFR recycling, but the figure caption identifies panel D as an LDLR endocytosis assay. The TFR recycling assay is panel E.
“Finally, kinetic experiments confirmed a delay in TFR recycling to the plasma membrane (Fig. 6D).”
“E: TFR recycling was assayed by synchronizing cells with internalized transferrin and tracking the reduction in fluorescent signal at indicated time points by flow cytometry.”
Discussion cites a nonexistent Fig. 4I panel
MinorThe discussion cites Fig. 4H-I, but the Fig. 4 caption lists panel H as its final panel.
“RAB10 depletion also caused an intracellular accumulation of both receptors in recycling organelles consistent with a delay in their plasma membrane recycling (Figs. 4H–I and 5G, H).”
“H: Mander’s overlap of LDLR with each indicated marker.”
Discussion cites a nonexistent Fig. 5H panel
MinorThe discussion cites Fig. 5H, but the Fig. 5 caption lists panel G as its final panel.
“RAB10 depletion also caused an intracellular accumulation of both receptors in recycling organelles consistent with a delay in their plasma membrane recycling (Figs. 4H–I and 5G, H).”
“G: Mander’s overlap of TFR with each indicated marker.”
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RABIF promotes hepatocellular carcinoma progression through regulation of mitophagy and glycolysis
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Systematic elucidation of genetic mechanisms underlying cholesterol uptake
Hamilton, M. C., Fife, J. D., Akinci, E., Yu, T., Khowpinitchai, B., Cha, M., Barkal, S., Thi, T. T., Yeo, G. H. T., Ramos Barroso, J. P., et al. (2023) · Cell Genomics · doi:10.1016/j.xgen.2023.100304 · Cited by 16
Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation
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Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening
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Metadata
- Authors
- Khan, T. G., Ginsburg, D., & Emmer, B. T.
- Affiliations
- University of Michigan (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ginsburg, David
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 63
- Issue
- 8
- Pages
- 100248
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC9305350
- OpenAlex
- W4283373848
- Cited by
- 21
- References
- 52
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 5 · 2023: 5
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- 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 › Autophagy in Disease and Therapy
- Keywords
- Rab10, small GTPases, LDL receptor, transferrin receptor, endosomal recycling, hepatocytes, LDL uptake, iron transport, atherosclerosis, Huh7 cells
- MeSH terms
- Endocytosis, Lipoproteins, LDL, Receptors, LDL, Receptors, Transferrin, Endosomes, Transferrin, Monomeric GTP-Binding Proteins, rab GTP-Binding Proteins, Hepatocytes
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 2026-11-08, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-08 (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 ›
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