Vps52 (CG7371) is the Drosophila ortholog of VPS52, a CATCHR-family subunit shared by two related multisubunit tethering complexes. Together with Vps51 and Vps53 it forms the core of the Golgi-associated retrograde protein (GARP) complex, which additionally contains Vps54 (scattered) and tethers endosome-derived carriers at the trans-Golgi network, and of the endosome-associated recycling protein (EARP) complex, which contains Vps50 (syndetin) in place of Vps54 and supports recycling of endocytosed cargo to the plasma membrane. In fly tissues a GFP-tagged Vps52 is a peripheral protein of the trans-Golgi network whose Golgi recruitment is aided by the Arf-like GTPase Arl5, and in S2 cell lysates the Vps51-Vps52-Vps53 core binds the GTP-bound forms of Rab4 and Arl5. Like other GARP/EARP subunits it engages SNAREs to promote vesicle tethering and fusion.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000938 GARP complex | IBA GO_REF:0000033 | ACCEPT | Summary: Vps52 is a core subunit of the GARP tethering complex. Reason: Vps52 is a conserved core subunit of GARP (shared with EARP); the IBA/NAS rows agree with the direct fly evidence that Vps52 co-purifies with the other three GARP subunits. Supporting Evidence: PMID:25795912 Amongst the more abundant proteins that bound specifically to Arl5-GTP were the Drosophila orthologues of the four subunits of the GARP complex PMID:25795912 This implies that the exogenous Vps52-GFP is being incorporated into the GARP complex |
| GO:0000938 GARP complex | IDA PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | ACCEPT | Summary: Vps52 is a core subunit of the GARP tethering complex. Reason: The fly Vps51-Vps52-Vps53 core co-purifies with Vps54/scat on GTP-locked Arl5 and Rab columns, and tagged Vps52 localizes to the trans-Golgi network where GARP acts. GARP membership is the defining property of Vps52. Supporting Evidence: PMID:25795912 Amongst the more abundant proteins that bound specifically to Arl5-GTP were the Drosophila orthologues of the four subunits of the GARP complex PMID:25795912 This implies that the exogenous Vps52-GFP is being incorporated into the GARP complex |
| GO:0000938 GARP complex | NAS PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | ACCEPT | Summary: Vps52 is a core subunit of the GARP tethering complex. Reason: Vps52 is a conserved core subunit of GARP (shared with EARP); the IBA/NAS rows agree with the direct fly evidence that Vps52 co-purifies with the other three GARP subunits. Supporting Evidence: PMID:25795912 Amongst the more abundant proteins that bound specifically to Arl5-GTP were the Drosophila orthologues of the four subunits of the GARP complex PMID:25795912 This implies that the exogenous Vps52-GFP is being incorporated into the GARP complex |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | MODIFY | Summary: Golgi localization; correct but less specific than trans-Golgi network. Reason: Vps52-GFP localizes specifically to the trans-Golgi network in fly tissues; the more specific term trans-Golgi network (GO:0005802) is already annotated to Vps52 by IDA (PMID:25795912) and should replace the generic Golgi apparatus term. Proposed replacements: trans-Golgi network Supporting Evidence: PMID:25795912 Drosophila Vps52 localizes to the TGN. |
| GO:0005794 Golgi apparatus | ISS GO_REF:0000024 | MODIFY | Summary: Golgi localization; correct but less specific than trans-Golgi network. Reason: Vps52-GFP localizes specifically to the trans-Golgi network in fly tissues; the more specific term trans-Golgi network (GO:0005802) is already annotated to Vps52 by IDA (PMID:25795912) and should replace the generic Golgi apparatus term. Proposed replacements: trans-Golgi network Supporting Evidence: PMID:25795912 Drosophila Vps52 localizes to the TGN. |
| GO:0005802 trans-Golgi network | IDA PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | ACCEPT | Summary: Vps52-GFP localizes to the trans-Golgi network in fly tissues. Reason: Direct localization in salivary gland duct and follicle cells. Supporting Evidence: PMID:25795912 Drosophila Vps52 localizes to the TGN. |
| GO:0005829 cytosol | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Cytosolic pool of a peripheral membrane complex. Reason: GARP subunits cycle between membrane-bound and cytosolic pools; a cytoplasmic pool of Vps52-GFP is seen and increases when Arl5 is absent. The functional location is the TGN membrane, so cytosol is non-core. Supporting Evidence: PMID:25795912 Removal of Arl5 reduced the intensity of Vps52-GFP on the Golgi and there was a substantial increase in the amount of GFP in the cytoplasm |
| GO:0007041 lysosomal transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Lysosomal transport inferred phylogenetically. Reason: GARP is required indirectly for delivery of lysosomal hydrolases because it retrieves their sorting receptors from endosomes to the TGN; fly Arl5 mutants that partially displace GARP have enlarged late endosomes/lysosomes. Lysosomal transport is a downstream consequence rather than the step Vps52 performs. IBA donors are human VPS52 (Q8N1B4, PTN001021633). Supporting Evidence: PMID:25795912 In Drosophila tissues the GARP complex is partially displaced from the Golgi when Arl5 is absent, and the late endosomal compartment is enlarged. |
| GO:0019905 syntaxin binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Syntaxin binding inferred from mammalian VPS52 and the PANTHER family. Reason: GARP and EARP engage Qa/Qc SNAREs such as syntaxin 6 as part of their tethering mechanism, and this is a plausible conserved property, but it has not been tested for fly Vps52 and is better represented at the level of the assembled complex's tethering activity. IBA donors are human VPS52 (Q8N1B4) and C. elegans vps-52 (PTN000367098); ISS from human VPS52. Supporting Evidence: PMID:25799061 EARP interacts with the target SNARE syntaxin 6 and various cognate SNAREs. |
| GO:0019905 syntaxin binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Syntaxin binding inferred from mammalian VPS52 and the PANTHER family. Reason: GARP and EARP engage Qa/Qc SNAREs such as syntaxin 6 as part of their tethering mechanism, and this is a plausible conserved property, but it has not been tested for fly Vps52 and is better represented at the level of the assembled complex's tethering activity. IBA donors are human VPS52 (Q8N1B4) and C. elegans vps-52 (PTN000367098); ISS from human VPS52. Supporting Evidence: PMID:25799061 EARP interacts with the target SNARE syntaxin 6 and various cognate SNAREs. |
| GO:0031267 small GTPase binding | IPI PMID:25453831 Toward a comprehensive map of the effectors of rab GTPases. | ACCEPT | Summary: Vps52-containing GARP complex binds GTP-bound Rab4 (and Arl5) in fly cell lysates. Reason: Rab affinity chromatography of S2 cell lysates recovered Vps51, Vps52 and Vps53 specifically on GTP-locked Rab4, and binding of tagged Vps52 (CG7371-GFP) was confirmed to be GTP specific. This Rab/Arl effector binding is how the complex is recruited to its target membranes. Supporting Evidence: PMID:25453831 Most striking were Vps51, Vps52, and Vps53, three subunits of the GARP tethering complex that is found on the Golgi and involved in retrograde traffic from endosomes PMID:25453831 we were able to confirm that GARP subunit binding is GTP specific |
| GO:0032456 endocytic recycling | IBA GO_REF:0000033 | ACCEPT | Summary: Vps52 is a shared subunit of EARP, which mediates endocytic recycling. Reason: Vps52 is part of both GARP and EARP; EARP (with Vps50/syndetin) acts in recycling of internalized transferrin receptor to the cell surface. The fly Vps50-Vps52-Vps53 association (GARPII/EARP) supports conservation of this role. IBA donors include fly Vps52 itself and human VPS52 (Q8N1B4). Supporting Evidence: PMID:25799061 Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. PMID:25453831 These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996 |
| GO:0032456 endocytic recycling | IDA PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | MODIFY | Summary: The cited fly study tests endosome-to-Golgi traffic, not recycling to the plasma membrane. Reason: PMID:25795912 shows that Vps52-GFP is a TGN-resident GARP subunit whose recruitment depends on Arl5, consistent with endosome-to-Golgi retrograde traffic; it does not assay recycling of internalized cargo to the plasma membrane, which is what GO:0032456 describes. The process supported by this paper is retrograde transport, endosome to Golgi. Proposed replacements: retrograde transport, endosome to Golgi Supporting Evidence: PMID:25795912 These phenotypes are consistent with a role in endosome-to-Golgi traffic, but are less severe than loss of GARP itself. |
| GO:0032456 endocytic recycling | ISS GO_REF:0000024 | ACCEPT | Summary: Vps52 is a shared subunit of EARP, which mediates endocytic recycling. Reason: Vps52 is part of both GARP and EARP; EARP (with Vps50/syndetin) acts in recycling of internalized transferrin receptor to the cell surface. The fly Vps50-Vps52-Vps53 association (GARPII/EARP) supports conservation of this role. IBA donors include fly Vps52 itself and human VPS52 (Q8N1B4). Supporting Evidence: PMID:25799061 Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. PMID:25453831 These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996 |
| GO:0032456 endocytic recycling | NAS PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | ACCEPT | Summary: Vps52 is a shared subunit of EARP, which mediates endocytic recycling. Reason: Vps52 is part of both GARP and EARP; EARP (with Vps50/syndetin) acts in recycling of internalized transferrin receptor to the cell surface. The fly Vps50-Vps52-Vps53 association (GARPII/EARP) supports conservation of this role. IBA donors include fly Vps52 itself and human VPS52 (Q8N1B4). Supporting Evidence: PMID:25799061 Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. PMID:25453831 These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996 |
| GO:0042147 retrograde transport, endosome to Golgi | IBA GO_REF:0000033 | ACCEPT | Summary: Vps52, as part of GARP, tethers endosome-derived vesicles at the TGN. Reason: Core process of the GARP complex. In flies GARP is recruited to the TGN by Arl5, and loss of Arl5 gives phenotypes consistent with an endosome-to-Golgi defect. Supporting Evidence: PMID:25795912 complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN) |
| GO:0042147 retrograde transport, endosome to Golgi | NAS PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | ACCEPT | Summary: Vps52, as part of GARP, tethers endosome-derived vesicles at the TGN. Reason: Core process of the GARP complex. In flies GARP is recruited to the TGN by Arl5, and loss of Arl5 gives phenotypes consistent with an endosome-to-Golgi defect. Supporting Evidence: PMID:25795912 complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN) |
| GO:0055037 recycling endosome | ISS GO_REF:0000024 | ACCEPT | Summary: Recycling endosome localization by similarity to the EARP subunit VPS52. Reason: As a shared EARP subunit, Vps52 is expected on recycling endosomes; EARP localization to recycling endosomes is determined by its syndetin/Vps50 subunit. Supporting Evidence: PMID:25799061 This change determines differential localization of EARP to recycling endosomes and GARP to the Golgi complex. |
| GO:1990745 EARP complex | IPI PMID:25453831 Toward a comprehensive map of the effectors of rab GTPases. | NEW | Summary: Vps52 associates with the Vps50 (CG4996/Vps54L) subunit that defines the fly EARP (GARPII) complex. Reason: GFP-CG4996/Vps50 co-precipitated Myc-tagged Vps52 (CG7371) and Vps53 from S2 cells, and the four proteins co-purified on Rab4 and Rab14 columns, defining a Vps54-free version of GARP that corresponds to EARP. Vps51 already carries EARP complex by IBA; adding it here keeps the shared core subunits consistent. Supporting Evidence: PMID:25453831 These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996 PMID:25799061 The two complexes share the Ang2, Vps52 and Vps53 subunits |
| GO:7770062 vesicle membrane tethering activity | TAS PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | NEW | Summary: Vps52 contributes to the vesicle-tethering activity of the GARP complex. Reason: GARP is a multisubunit tethering complex that captures endosome-derived vesicles at the TGN; Vps52 is a subunit, so the activity is recorded as contributes_to. This matches the replacement used for the ND molecular_function rows of Vps50, Vps51 and Vps53, and the core function already uses this term. Supporting Evidence: PMID:25795912 complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN) |
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Download this section (compressed HTML)Q: Do fly Vps52 loss-of-function mutants disrupt recycling of endocytosed cargo to the plasma membrane as well as retrieval of the M6PR homolog Lerp to the TGN, i.e. are both the GARP and EARP roles conserved in Drosophila tissues?
Experiment: Compare Lerp (M6PR) localization and transferrin-receptor-like cargo recycling in Vps52, scat (Vps54) and Vps50 mutant or RNAi tissues to separate GARP- and EARP-dependent functions of the shared Vps52 subunit.
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