The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index; 14 of the 20 sources its claims cite were checked for support.
The sortilin cytoplasmic tail conveys Golgi–endosome transport and binds the VHS domain of the GGA2 sorting protein
Open accessAbstract
Sortilin belongs to a growing family of multiligand type-1 receptors with homology to the yeast receptor Vps10p. Based on structural features and sortilin's intracellular predominance, we have proposed it to be a sorting receptor for ligands in the synthetic pathway as well as on the cell membrane. To test this hypothesis we examine here the cellular trafficking of chimeric receptors containing constructs of the sortilin tail. We report that sorting signals conforming to YXX and dileucine motifs mediate rapid endocytosis of sortilin chimeras, which subsequently travel to the trans-Golgi network, showing little or no recycling. Furthermore, we found that cation-independent mannose 6-phosphate receptor (MPR300)-sortilin chimeras, expressed in mannose 6-phosphate receptor knockout cells, were almost as efficient as MPR300 itself for transport of newly synthesized beta-hexosaminidase and beta-glucuronidase to lysosomes, and established that the sortilin tail contains potent signals for Golgi-endosome sorting. Finally, we provide evidence suggesting that sortilin is the first example of a mammalian receptor targeted by the recently described GGA family of cytosolic sorting proteins, which condition the Vps10p-mediated sorting of yeast carboxypeptidase Y.
Overview
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Written from the paper’s full text.
TL;DR
The sortilin cytoplasmic tail contains endocytic and Golgi–endosome sorting signals that direct chimeric receptors to the trans-Golgi network and can substitute for the MPR300 tail in lysosomal enzyme transport. Sortilin binds the GGA2 sorting protein via its VHS domain, and this interaction requires the C-terminal dileucine motif.
Key findings
- Endocytosis of IL2R–sortilin chimeras depends mainly on the YXXF motif Y14SVL17 and, to a lesser extent, the C-terminal dileucine L51L52. At 30 min, non-internalized tracer was 41.5 ± 6.3% for wild-type tail, 76.5 ± 4.5% for Y14A/L17A, and 90.5 ± 1.2% for Y14A/L17A plus deletion of L51L52; combined disruption accounted for ~80% reduction in endocytosis.
- Internalized IL2R–sortilin-wt traveled through clathrin-coated vesicles and Lamp-1-negative early endosomes to the TGN, co-localizing with TGN38 at 60 min, with little or no recycling over 4 h.
- MPR300–sortilin-wt chimeras in mannose 6-phosphate receptor-deficient (mpr−) cells corrected secretion of newly synthesized β-hexosaminidase and β-glucuronidase and normalized lysosome morphology. At optimal expression, medium from transfected cultures contained ~80% less β-hexosaminidase than untransfected cells; with mannose 6-phosphate, <40% of the enzyme was found in the medium.
- Sortilin binds GGA2 via the GGA2 VHS domain; >10% of the labeled sortilin pool was precipitated by GST–GGA2s, and deletion of the C-terminal dileucine abolished the interaction in two-hybrid and pull-down assays.
Methods
- Chimeric receptors were generated by combining the sortilin cytoplasmic domain (wild-type or mutated/deleted at candidate motifs) with the luminal and transmembrane domains of IL2Rα (CD25/Tac) or MPR300. IL2R–sort chimeras were expressed in CHO-K1 cells; MPR300–sort chimeras were expressed in mouse embryonic fibroblasts deficient in both mannose 6-phosphate receptors (mpr−).
- Endocytosis was measured with 125I-labeled anti-Tac/anti-CD25 and acid wash (pH 2.5); trafficking was analyzed by confocal and electron microscopy, surface biotinylation/metabolic labeling, and β-hexosaminidase fluorometric assays in the absence or presence of mannose 6-phosphate.
- Protein interactions were tested by yeast two-hybrid screening with sortilin cytoplasmic domain as bait and by GST pull-down assays using GGA2 constructs, including the VHS domain and GAEH domain.
Limitations
- The paper states that evidence for PACS-1 involvement and for the acidic cluster in sortilin trafficking was inconclusive; cell-to-cell variation was not insignificant and further evidence was needed. Full-length GGA2 could not be purified as a uniform protein.
- Evident from the text: conclusions rely on chimeric receptors and antibody–receptor complexes, which may not fully reflect full-length sortilin behavior; several assays used transfected cells with varying expression levels and clone-to-clone differences.
- No in vivo validation is reported.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
14 of 20 cited sources checked · 7 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This is in good agreement with previous evidence on sortilin and MPR300 co-localization, and in strong support of full-length sortilin as a functional sorting receptor (Petersen et al., 1997;Morris et al., 1998).”
What the sources say
- Partly supportedcites Petersen et al., 1997 sourceExperimental — accuracy not yet measured
The section headed “Transient Expression of gp95/Sortilin and Chimeric Receptors” (page not provided) reports co-localization with the CI-M6P receptor for a chimera bearing sortilin’s cytoplasmic tail, not for full-length sortilin. The paper describes sortilin as a candidate sorting receptor; it does not establish that the full-length protein functions as one. (LLM, conf=0.87)
- Partly supportedcites Morris et al., 1998 sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports that sortilin appears to colocalize with CIM6PR (MPR300) in COS cells and says this suggests a sorting-receptor role. The Discussion (page unavailable) says sortilin’s function remains undetermined and that it could instead be a receptor for an extracellular ligand. The source therefore supports the prior colocalization and the proposed role, but not an established function for full-length sortilin as a sorting receptor. (LLM, conf=0.86)
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“whereas that of Pep12p is not”
What the sources say
- Supportedcites Black and Pelham, 2000 source
The Abstract (page unavailable) reports that Pep12p sorting was defective in cells lacking either the clathrin heavy or light chain. This supports the claim that Pep12p sorting is not clathrin independent. (LLM, conf=0.92)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Thus, Vps10p-mediated sorting of CPY is impaired in gga null cells (Hirst et al., 2000)”
What the sources say
- Supportedcites Hirst et al., 2000 source
The Results (Yeast Homologues of the GGAs) identify Vps10p as the receptor that transports pro-CPY and report a significant CPY-sorting defect in cells lacking both GGA genes. The same section reports that these cells secrete CPY, confirming missorting rather than merely delayed processing. The finding concerns the double knockout; either single knockout showed no obvious defect. (LLM, conf=0.91)
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
“Accordingly, during a 4 h chase at 37°C, little or no internalized 125 I-labelled anti-Tac returned to the surface in a pH 2.5-releasable form.”
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, it should be noted that chimeras carrying Y 14 A as a single mutation showed no signs of missorting.”
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
“since L 51 A/L 52 A had little impact on the cellular uptake, in agreement with ®ndings in CHO cells”
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, missorting by double mutants (Y 14 A/L 17 A) was profound even at high receptor expression levels.”
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 cultures supplemented with mannose 6-phosphate, <40% of the enzyme was found in the medium.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The MPR300-sort chimeras bind the mannose 6-phosphate moieties of proenzymes via the MPR300 luminal domain.
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
“Furthermore, we found that cation-independent mannose 6-phosphate receptor (MPR300)±sortilin chimeras, expressed in mannose 6-phosphate receptor knockout cells, were almost as ef®cient as MPR300 itself for transport of newly synthesized b-hexosaminidase and b-glucuronidase to lysosomes”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The MPR300-sort chimeras bind the mannose 6-phosphate moieties of proenzymes via the MPR300 luminal domain.
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 ®nding that chimeric receptors lacking the C-terminal dileucine fail to interact with GGA2”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 11
- It may state two separate claims as one. 30
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Since sorting of CPY is clathrin independent, i.e. restores in the absence of functional clathrin heavy chains (Seeger and Payne, 1992)”
What the sources say
- Partly supportedcites Seeger and Payne, 1992 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says CPY delivery can occur without functional clathrin heavy chain, and the Results report improved sorting after 3 hours at 37°C. But the paper also reports a rapid, severe sorting defect when clathrin function is first impaired. Calling CPY sorting simply clathrin independent omits that qualification. (LLM, conf=0.88)
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“GGA2 belongs to a recently described family of monomeric cytosolic proteins that includes three mammalian and two (gga) yeast members (Boman et al., 2000;Dell'Angelica et al., 2000;Hirst et al., 2000;Poussu et al., 2000;Takatsu et al., 2000).”
What the sources say
- Not checked — no full text of the sourcecites Boman et al., 2000 source
- Partly supportedcites Dell'Angelica et al., 2000 sourceExperimental — accuracy not yet measured
The Results sections identify GGA2 as one of three human GGAs, alongside two yeast counterparts, and report that most endogenous GGA2 was in a cytosolic fraction. However, the biochemical characterization says its sedimentation is compatible with either a monomer or an asymmetrically shaped dimer; it does not establish that GGA2 is monomeric. (LLM, conf=0.88)
- Supportedcites Hirst et al., 2000 source
The Discussion (page not provided) identifies GGA2 as one of at least three mammalian GGAs and names two yeast members. The Results report GGA2 in cytosolic fractions at an apparent size of about 75 kD, consistent with it not being part of a large protein complex; they also show that it cycles between cytosol and membranes. (LLM, conf=0.90)
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. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Information concerning their physiological function is still limited, but important ®ndings in yeast convincingly implicate the family in Golgi±endosome/lysosome transport.”
What the sources say
- Supportedcites Hirst et al., 2000 source
The Discussion reports that deleting both yeast GGA genes causes missorting of a vacuolar protein, providing strong evidence for a role in protein delivery to the vacuole. It also concludes, from yeast and mammalian findings together, that GGAs facilitate trafficking from late Golgi membranes toward the vacuole or lysosome. Page numbers were not supplied. (LLM, conf=0.94)
- Supportedcites Black and Pelham, 2000 source
The Introduction states that Gga1p or Gga2p is required for a yeast sorting pathway and that the authors’ data indicate transport from the Golgi to late endosomes. The Results report that deleting both yeast GGA genes abolished sorting through that pathway, supporting the claim that the family is implicated in Golgi–endosome transport. (LLM, conf=0.94)
Strength:boosted· not yet calibratedCausal:correlational· 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“and the incorporation of the syntaxin Pep12p in late endosomes is likewise dependent on gga proteins (Black and Pelham, 2000).”
What the sources say
- Supportedcites Black and Pelham, 2000 source
The Abstract states that Pep12p is primarily located in late endosomes and that its sorting is abolished when both Gga1p and Gga2p are absent. The Introduction likewise describes the Pep12p pathway to late endosomes as dependent on the presence of Gga1p or Gga2p. (LLM, conf=0.93)
Strength:plain· not yet calibratedCausal:direct· 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In any case, both types of motif mediate binding to AP complexes involved in budding of TGN transport vesicles (AP-1 and -3) as well as endocytosis (AP-2) (reviewed in Bonifacino and Dell'Angelica, 1999;Kirchhausen, 1999).”
What the sources say
- Partly supportedcites Bonifacino and Dell'Angelica, 1999 sourceExperimental — accuracy not yet measured
The sections on AP μ-subunit interactions and physiological roles report that YXXØ motifs interact with AP-1, AP-2, and AP-3; they associate AP-1 with the TGN and AP-2 with internalization. The section on recognition by AP-2 says dileucine motifs bind AP-1 and AP-2 β subunits, but does not establish binding to AP-3. It also says AP-3’s localization is uncertain, with evidence suggesting endosomes and/or the TGN. Page numbers are unavailable in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites Kirchhausen, 1999 source
Strength:plain· not yet calibratedCausal:direct· 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Only a minor fraction of the receptors is expressed on the cell surface, whereas ~90% are found in Golgi and vesicles, showing extensive co-localization with MPR300 (Petersen et al., 1997;Morris et al., 1998).”
What the sources say
- Partly supportedcites Petersen et al., 1997 sourceExperimental — accuracy not yet measured
In “Transient Expression of gp95/Sortilin and Chimeric Receptors” (page unavailable), full-length sortilin localized particularly to the Golgi, with no detectable cell-surface staining. A receptor bearing sortilin’s tail co-localized with the cation-independent mannose-6-phosphate receptor in the Golgi and endosome-like vesicles. The paper does not report that approximately 90% of sortilin is in those compartments, and the co-localization experiment used a chimeric receptor rather than full-length sortilin. (LLM, conf=0.88)
- Partly supportedcites Morris et al., 1998 sourceExperimental — accuracy not yet measured
The Abstract says sortilin is largely located in intracellular GLUT4-containing vesicles in adipocytes and reports apparent co-localization with the cation-independent mannose 6-phosphate receptor in COS cells. The results on vesicle isolation report 70–75% of sortilin in the sampled fraction in GLUT4 vesicles, not that ~90% of all sortilin is in Golgi and vesicles; the paper also does not quantify the fraction at the cell surface. Pages are not specified in our copy. (LLM, conf=0.87)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“GGAs are ARF dependent and Golgi localizing, and comprise, from the N-terminus, a VHS domain, a so-called GAT domain, a linker region and a C-terminal GAEH domain (Dell'Angelica et al., 2000).”
What the sources say
- Supportedcites Dell'Angelica et al., 2000 source
The Introduction identifies GGAs as Golgi-localized, ARF-binding proteins, describes their ARF-dependent association with the TGN, and lists the four regions in N- to C-terminal order. The Results section, “Identification and Domain Organization of GGA Proteins,” names the C-terminal region GAE. No page numbers are provided in our copy. (LLM, conf=0.94)
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. It may state two separate claims as one.
- 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 results demonstrate that neither fulllength sortilin nor the chimeric receptor was precipitated upon incubation with the C-terminal GAEH construct (Figure 8C and D).”
Load-bearingStrength:boosted· 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
“In control experiments, both full-length GGA2 and GGA2s induced a positive response with sortilin-cd as bait (data not shown).”
Strength:plain· not yet calibratedCausal:correlational· 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
“Internalized IL2R±sort-wt chimeras are directed to the TGN without recycling”
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 time course of [ 125 I]anti-Tac internalization by IL2R±sort chimeras is delineated in Figure 2 and clearly designates Y 14 SVL 17 as the main signal for endocytosis, being responsible for ~60% of the activity, and the tyrosine as the single most important residue.”
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
“Neither the acidic cluster (H 44 ±D 50 ) nor S 41 GY 43 (a signal in Lamp-1 and -2) appears to constitute active signals in sortilin.”
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
“In accordance, GST±VHS mediated precipitation of a considerable fraction of the IL2R±sort-wt contained in CHO lysates but produced little or no pull-down of the IL2R±sort-del L 51 L 52 (Figure 9B).”
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 translated product of the isolated clone (GGA2s) therefore represents a truncated form of GGA2, which contains the ®rst 193 N-terminal residues of the published GGA2 sequence, including the entire VHS domain, followed by the amino acid sequence LFLSASEPGPIHFPSTMNSPNRYSLDISI.”
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
“Following internalization in coated pits, chimeric receptors (and full-length sortilin) travel to the TGN seemingly by a route bypassing Lamp-1-positive (late) endosomes.Internalized receptors, at least when complexed with antibodies, show little or no recycling.”
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
“we have demonstrated that the sortilin cytoplasmic domain conveys endocytosis and TGN localization as well as transport from the synthetic pathway to lysosomes”
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 results (Figure 9A) demonstrate that constructs not containing the C-terminal dileucine failed to induce a response in yeast cells (blue staining), suggesting that disruption of this motif abolished proper binding of GGA2.”
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
“Among the resulting con®rmed positive clones, which did not include any adaptor protein (m) subunits, one was found to be a differentially spliced version of human GGA2 cDNA (DDBJ/EMBL/GenBank accession No. AF323754).”
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 contrast, the splice variant GGA2s construct mediated pull-down, in intra-(data not shown) as well as extracellular buffer, of both sortilin and IL2R±sort-wt (e.g. Figure 8C)”
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
“SDS±PAGE analysis (Figure 6, left panel inset) demonstrates that while b-glucuronidase was released into the medium in its proform, the cells contained only the converted mature enzyme, providing evidence that retained (not secreted) enzyme had been directed to the lysosomes.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The MPR300-sort chimeras bind the mannose 6-phosphate moieties of proenzymes via the MPR300 luminal domain.
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
“Using this method, a maximum of ~67% of the total amount of anti-Tac bound by IL2R±sort-wt was internalized within 2 h, which is similar to the amount (~75%) of labelled antisortilin internalized by CHO cells expressing full-length sortilin (data not shown).”
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
“Using this approach, we found that the fraction of mutant receptors exposed on the plasma membrane was 1.3-(L 51 L 52 deleted), 2.8-(Y 14 A/L 17 A) and 3.8-(the two combined) fold higher than that of IL2R±sort-wt.”
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
“but, surprisingly, only L 17 A and not Y 14 A had a clear impact on intracellular transport.”
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 60 min, staining predominated in vesiculotubular structures in close proximity to the nucleus, and double staining demonstrated that the antibody±receptor complexes to a large extent co-localized with TGN38 (Figure 4, panel 3).”
- Also stated in: § Endocytosis of chimeric receptors · plain
“It is remarkable that co-localization with Lamp-1 was scarce and only seen upon prolonged incubation (>45 min).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Endocytosis of chimeric receptors · plain
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
“It follows that in terms of sorting from the synthetic pathway, L 17 may be a key residue, but tyrosine and the YXXF motif as such are not functionally signi®cant.”
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
“From ®ndings obtained in the absence and presence of mannose 6-phosphate, it can further be deduced that the dileucine almost only contributes to the direct intracellular transport, whereas residues of the YXXF motif promote transport by endocytosis as well as by sorting from the Golgi”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Owing to their receptor de®ciency, these (mpr ± ) cells are unable to transfer newly synthesized lysosomal enzymes, normally targeted by the mannose 6-phosphate receptors, from the secretory pathway to the late endosomes.The cells consequently release the ligands into the medium and are left with abnormal lysosomes.”
What the sources say
- Not checked — no full text of the sourcecites Pohlmann et al., 1995 source
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
“The ®ndings establish that sortilin-cd has the capacity for Golgi±endosome sorting and the evidence is that this function relies on sorting motifs other than those governing endocytosis.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“False positives were identi®ed and eliminated by co-transforming EGY48[p8op-lacZ] cells with the rescued library plasmids as well as bait plasmids without insert or with a non-interacting insert.”
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
“Thus, unlike the cytoplasmic domains of other transmembrane proteins residing in the TGN, e.g.TGN38 and furin (D.Kasper and R.Pohlmann, unpublished results), the sortilin-cd can substitute for the MPR300-cd and provide direct transport to lysosomes for ligands bound in the synthetic pathway as well as on the plasma membrane.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The MPR300-sort chimeras bind the mannose 6-phosphate moieties of proenzymes via the MPR300 luminal domain.
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
“It can be concluded from the above that sortilin-cd mediates endocytosis of IL2R±sort-wt in clathrin-coated vesicles, avoids recycling and directs the receptors to the TGN via Lamp-1-negative endosomes.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Blue colonies were subcloned three times to eliminate noninteracting plasmids.”
Strength:plain· not yet calibratedCausal:direct· 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.
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, as demonstrated by the two-hybrid screen and pull-down experiments involving sortilin and GGA2, alternative transporter molecules may target the sortilin tail.”
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
“demonstrates that in addition to endocytosis the sortilin cytoplasmic domain conveys Golgi localization and Golgi±endosome transport.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Sortilin belongs to a growing family of multiligand type-1 receptors with homology to the yeast receptor Vps10p.”
What the sources say
- Not checked — no full text of the sourcecites Marcusson et al., 1994 source
Strength:plain· not yet calibratedCausal:correlational· 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The correct composition of the above constructs was ensured by sequencing in a Licore 4200 or the ABI 373A system (MWG, Germany).”
Strength:plain· not yet calibratedCausal:direct· 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.
Mannose 6-phosphate inhibits ligand binding at the cell surface and prevents uptake from the medium.
“Since mannose 6-phosphate inhibits ligand binding at the cell surface and thereby prevents uptake from the medium, it follows that the chimeric receptor, similarly to MPR300 itself, downregulates the cellular secretion of b-hexosaminidase.”
The paper relies on this without support.
The MPR300-sort chimeras bind the mannose 6-phosphate moieties of proenzymes via the MPR300 luminal domain.
“Since these chimeras (MPR300±sort) bind the mannose 6-phosphate moieties of proenzymes via the MPR300 luminal domain, we were then able to determine their sorting by monitoring the fate and cellular release of ligands, i.e. b-hexosaminidase.”
The paper relies on this without support.
Sortilin is similar to the CPY sorting receptor Vps10p.
“in view of the similarity between sortilin and the CPY sorting receptor Vps10p”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Sortilin is a lysosomal sorting protein that binds ligands both in the Golgi apparatus and at the plasma membrane and traffics them to the lysosome.”
From Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism (2012) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Sortilin localizes primarily to the Golgi apparatus”
From Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism (2012) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Sort.Stop was predominantly either secreted or in an intracellular, nonlysosomal location, while Sort.LAYA localized disproportionately to the plasma membrane (Supplemental Figure 4, A-D), consistent with previous observations (6).”
From Hepatic sortilin regulates both apolipoprotein B secretion and LDL catabolism (2012) · cites this paper as [6]
Experimental — accuracy not yet measured
Citations
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Self-citationGolgi-to-phagosome transport of acid sphingomyelinase and prosaposin is mediated by sortilin
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Lysosomal enzyme trafficking: from molecular mechanisms to human diseases
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Self-citationPhosphoregulation of sorting signal–VHS domain interactions by a direct electrostatic mechanism
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Self-citationSortilin as a Regulator of Lipoprotein Metabolism
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Self-citationVPS10P Domain Receptors: Sorting Out Brain Health and Disease
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Self-citationThe interactomics of sortilin: an ancient lysosomal receptor evolving new functions.
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Self-citationAutophagy Is Required for Sortilin-Mediated Degradation of Apolipoprotein B100
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Endofin Recruits TOM1 to Endosomes
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Self-citation
Metadata
- Authors
- Nielsen, M. S., Madsen, P., Christensen, E. I., Nykjær, A., Gliemann, J., Kasper, D., Pohlmann, R., & Petersen, C. M.
- Affiliations
- Aarhus University (DK)
- Universität Hamburg (DE)
- University of Münster (DE)
- Corresponding author
- Nielsen, Morten S.
- Petersen, Claus M.
- Venue
- The EMBO Journal
- Published
- 2001-05-01
- Volume
- 20
- Issue
- 9
- Pages
- 2180-2190
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC125444
- OpenAlex
- W1997957892
- Semantic Scholar
- c8a98d3e68ff0ec3bb6a392554900f8f02118f76
- Cited by
- 457
- References
- 46
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 8 · 2023: 18 · 2022: 11 · 2021: 12 · 2020: 15 · 2019: 23 · 2018: 14 · 2017: 20 · 2016: 24 · 2015: 18 · 2014: 17 · 2013: 16 · 2012: 18
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Aarhus Universitet
- Aarhus Universitets Forskningsfond
- Novo Nordisk Fonden
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- sortilin, cytoplasmic tail, GGA2, VHS domain, endocytosis, YXXΦ motif, dileucine motif, trans-Golgi network, lysosomal sorting, mannose 6-phosphate receptor, beta-hexosaminidase, beta-glucuronidase, chimeric receptors, carboxypeptidase Y
- MeSH terms
- Sortilin, Amino Acid Sequence, Animals, Carrier Proteins, Cytoplasm, Endocytosis, Fungal Proteins, Golgi Apparatus, Cricetinae, Humans, Membrane Glycoproteins, Nerve Tissue Proteins, Protein Binding, Proteins, Receptors, Cell Surface, Endosomes, Recombinant Fusion Proteins, Transfection, Receptors, Interleukin-2, Gene Expression, CHO Cells, Protein Structure, Tertiary, Two-Hybrid System Techniques, Amino Acid Motifs, Protein Transport, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, Adaptor Proteins, Vesicular Transport
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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.
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