dpy-23 (also called apm-2) encodes the sole mu2 (AP50) subunit of the heterotetrameric AP-2 clathrin adaptor complex in Caenorhabditis elegans. Within AP-2 the mu subunit recognises tyrosine-based YxxPhi sorting signals in the cytoplasmic tails of membrane cargo and helps dock the complex on phosphatidylinositol-4,5-bisphosphate-containing plasma membrane, linking selected cargo to the clathrin coat during clathrin-mediated endocytosis. DPY-23 is expressed in essentially all tissues, localises to presynaptic terminals with clathrin and synaptobrevin, to the plasma membrane of scavenger coelomocytes, to phagocytic cups around apoptotic cell corpses and to the periciliary membrane compartment at the base of sensory cilia. Loss of mu2 destabilises the AP-2 complex and produces dumpy, uncoordinated and egg-laying defective animals; synaptic clathrin is mislocalised and synaptic vesicle number and evoked release are reduced, though vesicle recycling continues. Physiological cargoes include the Wntless orthologue MIG-14, whose AP-2-dependent internalisation in Wnt-producing cells is required for EGL-20/Wnt secretion (acting in Wnt-producing cells, DPY-23 is therefore needed non-autonomously for migration of the HSN neurons and the Q neuroblast descendants, for mab-5 activation in the QL lineage, for ALM/PLM polarity and for V5 asymmetric division), the phagocytic receptor CED-1 during apoptotic cell clearance, and membrane retrieved at the ciliary base that sets ciliary membrane volume. Mu2 is largely dispensable for yolk uptake by oocytes, which depends more strongly on the alpha and beta2 subunits.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:23696751 Clathrin and AP2 are required for phagocytic receptor-mediat... | REMOVE | Summary: IPI protein-binding row from the apoptotic-cell-clearance study, in which 35S-labelled DPY-23 bound GST-CED-6 (and GST-DYN-1 and GST-LST-4) directly and DPY-23::GFP co-immunoprecipitated with endogenous CED-6 and with mCherry::LST-4 in vivo. Reason: The interaction with the CED-6 engulfment adaptor is well supported, but generic protein binding conveys no functional information. The biological content -- AP-2 acting as the clathrin-cargo adaptor that couples the CED-1 phagocytic receptor to clathrin during corpse clearance -- is already captured by the clathrin-cargo adaptor activity and endocytosis rows, and the CED-6 pull-down does not by itself demonstrate a distinct molecular function. Removal does not dispute the interaction. Supporting Evidence: PMID:23696751 GST-CED-6 directly interacted with 35S-labeled APA-2, APB-1 and DPY-23, and His6-tagged CHC-1C (Figure 4A). PMID:23696751 similar co-immunoprecipitation of DPY-23::GFP and GFP::CHC-1 with endogenous CED-6 was observed (Figure 4F and 4G). |
| GO:0005829 cytosol | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA cytosol from the AP-mu/stonin node PTN000242370 (seeded by human STON2). AP-2 has a soluble cytosolic pool that cycles onto the plasma membrane; the worm data show APM-2::GFP fluorescence throughout cells and residual alpha adaptin in mutants, consistent with a cytosolic pool, but the functional site is the plasma-membrane coated pit. Reason: A cytosolic pool of AP-2 is real and the phylogenetic inference is unobjectionable, but the activity of the mu2 subunit is exercised on the cytoplasmic face of the plasma membrane, so cytosol is recorded as a non-core location. Supporting Evidence: PMID:19047463 Thus, apm-2 is expressed in all tissues examined, which confirms and extends a previous paper claiming that apm-2 is expressed in neurons and some hypodermal cells (Shim and Lee, 2000). PMID:25303366 To measure the kinetics of membrane association we performed in vivo Fluorescence Recovery After Photobleaching (FRAP) on coelomocytes. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to plasma membrane. AP-2 is a peripheral protein of the cytoplasmic face of the plasma membrane; in the worm DPY-23::GFP is enriched at presynaptic varicosities and at the periciliary membrane compartment, and AP-2 alpha localises to the coelomocyte plasma membrane. Reason: Correct and core: the mu2 subunit docks AP-2 onto PI(4,5)P2-containing plasma membrane and recognises cargo there. Supporting Evidence: PMID:19047463 In particular, the ΞΌ2 subunit recruits cargo proteins containing the tyrosine-based YxxΟ motif (Owen and Evans, 1998) and mediates in part the association of the AP2 complex to membranes PMID:31259686 In wild-type animals, a DPY-23::GFP AP-2 ΞΌ2 subunit fusion protein was enriched at the PCMC of AWB in a domain similar to that occupied by TUB-1 |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (IPR001392 clathrin adaptor mu subunit; IPR018240 mu-homology domain) mapping to intracellular protein transport. AP-2-mediated internalisation of MIG-14/Wntless, CED-1 and synaptic vesicle proteins is protein transport from the plasma membrane into the cell. Reason: General but correct parent of the endocytic transport DPY-23 mediates; the more specific processes are carried by the experimental rows. Supporting Evidence: PMID:18160346 In dpy-23 mutants, MIG-14 accumulates at or near the plasma membrane. |
| GO:0006896 Golgi to vacuole transport | IBA GO_REF:0000033 | REMOVE | Summary: IBA from the deep AP-mu family node PTN000055849, whose experimental seeds for this term are yeast AP-1/AP-3 mu subunits and a mammalian non-AP-2 mu subunit acting between Golgi and vacuole/lysosome. AP-2 mu functions exclusively at the plasma membrane; there is no evidence that DPY-23 acts in Golgi-to-vacuole transport, and the worm literature places it at synapses, phagocytic cups, coelomocyte plasma membrane and the periciliary membrane. Reason: Over-propagation from a family-wide node that mixes AP-1/AP-3/AP-4 mu subunits (Golgi/endosome-to-vacuole carriers) with AP-2 mu (plasma-membrane endocytosis). The node placement is at the wrong depth for this term: the Golgi-to-vacuole role arose in the AP-1/AP-3 lineages, not at the common ancestor of all AP-mu subunits. DPY-23 loss affects plasma-membrane cargo (MIG-14 accumulating at the cell surface), not Golgi-derived trafficking. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000055849 SUPPORTS SOURCE BUT NOT TARGET Family-wide AP-mu node; the Golgi-to-vacuole evidence comes from non-AP-2 mu subunits and does not transfer to the plasma-membrane AP-2 paralog. SGD:S000000492 SUPPORTS SOURCE BUT NOT TARGET Yeast AP-1/AP-3 mu seed; Golgi/endosome-to-vacuole pathway, not endocytosis. SGD:S000001011 SUPPORTS SOURCE BUT NOT TARGET Yeast AP mu seed for vacuolar delivery. SGD:S000006180 SUPPORTS SOURCE BUT NOT TARGET Yeast AP mu seed for vacuolar delivery. UniProtKB:O00189 SUPPORTS SOURCE BUT NOT TARGET Mammalian non-AP-2 mu subunit acting on the TGN/endosome-to-lysosome route. Supporting Evidence: PMID:19047463 AP2 is the adaptor complex functioning during endocytosis at the plasma membrane (Mahaffey et al., 1990; Traub, 2003). PMID:18160346 In dpy-23 mutants, MIG-14 accumulates at or near the plasma membrane. |
| GO:0006898 receptor-mediated endocytosis | IMP PMID:18160346 C. elegans AP-2 and retromer control Wnt signaling by regula... | ACCEPT | Summary: dpy-23 mutants accumulate the Wntless orthologue MIG-14 at or near the plasma membrane of Wnt-producing cells, showing that AP-2 mu2 is required for internalisation of this membrane cargo; the paper explicitly frames DPY-23 as the mu subunit that mediates endocytosis of membrane proteins. Yolk-receptor uptake is only mildly reduced in apm-2 nulls, so the requirement is cargo-dependent. Reason: Direct genetic evidence that DPY-23 executes receptor/cargo internalisation at the plasma membrane, the defining activity of AP-2 mu2. Supporting Evidence: PMID:18160346 In dpy-23 mutants, MIG-14 accumulates at or near the plasma membrane. PMID:18160346 elegans gene dpy-23 encodes the ΞΌ subunit of the AP-2 clathrin adaptor complex that is necessary for receptor-mediated endocytosis and functions in several Wnt-related processes. PMID:19047463 Over 98% of the gonads in both apm-2(e840) and apm-2(gm17) mutants were scored as positive for yolk protein uptake |
| GO:0008021 synaptic vesicle | IBA GO_REF:0000033 | MODIFY | Summary: IBA synaptic vesicle from node PTN008307226, whose evidences include mammalian AP-2 mu detected on purified synaptic vesicles and the worm IDA itself (APM-2::GFP colocalising with synaptobrevin at synapses). AP-2 associates with the synaptic vesicle recycling pool and coated intermediates, but its activity is exercised at the presynaptic plasma membrane where vesicle proteins are retrieved. Reason: The phylogenetic inference reflects genuine association of AP-2 with vesicle fractions and synaptic varicosities across metazoa, but the vesicle itself is not the site of mu2 activity: AP-2 assembles coats on the presynaptic plasma membrane to retrieve vesicle proteins. A presynapse term captures what is conserved and is consistent with the treatment of the worm IDA on which this node partly rests. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN008307226 SUPPORTS SOURCE BUT NOT TARGET AP-2 mu node whose synaptic-vesicle evidence is colocalisation/co-purification of the adaptor with vesicle fractions; the conserved fact is presynaptic localisation, not vesicle residency. WB:WBGene00001082 Β· dpy-23 (Caenorhabditis elegans) SUPPORTS SOURCE BUT NOT TARGET The worm IDA itself, reviewed here as MODIFY to presynapse because the assay is light-microscopy colocalisation at varicosities. FB:FBgn0016975 SUPPORTS SOURCE BUT NOT TARGET Drosophila member with synaptic localisation evidence. MGI:MGI:1918272 SUPPORTS SOURCE BUT NOT TARGET Mouse member with synaptic-vesicle-fraction evidence. RGD:620135 Β· Ap2m1 (Rattus norvegicus) SUPPORTS SOURCE BUT NOT TARGET Rat AP-2 mu2 detected on purified synaptic vesicles. Proposed replacements: presynapse Supporting Evidence: PMID:19047463 APM-2β·GFP is localized at synapses and colocalizes with the synaptic vesicle protein synaptobrevin/VAMP PMID:19047463 These data indicate that ΞΌ2 associates with synaptic varicosities as predicted, but this localization is independent of other endocytosis proteins. |
| GO:0008021 synaptic vesicle | IDA PMID:19047463 Mu2 adaptin facilitates but is not essential for synaptic ve... | MODIFY | Summary: The IDA rests on confocal colocalisation of GABA-neuron APM-2::GFP with synaptobrevin::RFP and with RFP::CHC at synaptic varicosities. This resolves the protein to presynaptic terminals, and the authors describe it as association with synaptic varicosities; light-microscopy colocalisation with a vesicle marker cannot distinguish vesicle membrane from the surrounding presynaptic plasma membrane where AP-2 assembles coats. Reason: The evidence supports presynaptic localisation but not the specific claim that DPY-23 is a synaptic-vesicle component; the same paper shows APM-2::GFP colocalising equally with clathrin heavy chain and clathrin becoming mislocalised in mutants, i.e. the endocytic coat rather than the vesicle. A presynapse term states what the assay shows. Proposed replacements: presynapse Supporting Evidence: PMID:19047463 APM-2β·GFP is localized at synapses and colocalizes with the synaptic vesicle protein synaptobrevin/VAMP PMID:19047463 In addition, APM-2β·GFP colocalizes with C-terminal RFP-tagged clathrin heavy chain (CHC) at the synapse PMID:19047463 These data indicate that ΞΌ2 associates with synaptic varicosities as predicted, but this localization is independent of other endocytosis proteins. |
| GO:0010171 body morphogenesis | IMP PMID:10588660 Receptor-mediated endocytosis in the Caenorhabditis elegans ... | KEEP AS NON CORE | Summary: RNAi of mu2 (R160.1) produced severely dumpy progeny, the phenotype that gave dpy-23 its name; null alleles are likewise Dpy and rescued by the apm-2 genomic region. The dumpy body shape is a developmental consequence of losing AP-2-dependent endocytosis in the hypodermis rather than a process the adaptor executes directly. Reason: Robust phenotype, but body morphogenesis is a pleiotropic downstream outcome of the core endocytic function; keep as non-core. Supporting Evidence: PMID:10588660 All progeny of Ce- ΞΌ2(RNAi) and Ce- Ο2(RNAi) mothers were severely dumpy (Dpy). PMID:10588660 The similar Dpy phenotypes displayed in Ce- ΞΌ2(RNAi) and Ce- Ο2(RNAi) animals may indicate defects in hypodermal development. PMID:19047463 A 12-kb genomic PCR fragment (5 kb upstream, 5 kb coding sequence of ΞΌ2 adaptin, and 2 kb downstream) could fully rescue the dumpy, uncoordinated, and egg-laying defects of dpy-23(e840) and dpy-23(gm17) |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt keyword/subcellular mapping to membrane. AP-2 is a peripheral membrane protein of coated pits. Reason: Correct though general; the plasma membrane row is the informative one. Supporting Evidence: PMID:19047463 In particular, the ΞΌ2 subunit recruits cargo proteins containing the tyrosine-based YxxΟ motif (Owen and Evans, 1998) and mediates in part the association of the AP2 complex to membranes |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to vesicle-mediated transport; clathrin-mediated endocytosis is a form of vesicle-mediated transport. Reason: Correct high-level parent of the clathrin-dependent endocytosis rows. Supporting Evidence: PMID:19047463 Clathrin is recruited to endocytic sites on the plasma membrane by the AP2 adaptor complex. |
| GO:0030122 AP-2 adaptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA AP-2 adaptor complex. DPY-23 is the only mu2 subunit in the worm; its loss reduces alpha adaptin to 12-60% of wild type while residual alpha stays bound to sigma2, and mutations in all four subunits, including mu2, behave as a single functional unit in the FCHo bypass screen. Reason: Defining complex membership, supported by phylogeny, by co-dependence of subunit stability and by the shared mutant phenotype of apa-2, apm-2 and aps-2. Supporting Evidence: PMID:19047463 The reduction in Ξ± adaptin levels in both alleles indicates that ΞΌ2 is required to stabilize the AP2 complex; however, some residual Ξ± adaptin remains in the absence of ΞΌ2. PMID:25303366 A subsequent screen for bypass suppressors of fcho-1 nulls identified 71 compensatory mutations in all four AP2 subunits. |
| GO:0030131 clathrin adaptor complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to the parent term clathrin adaptor complex; AP-2 is a clathrin adaptor complex. Reason: Correct, if less specific than the AP-2 adaptor complex IBA. Supporting Evidence: PMID:19047463 Clathrin is linked to cargo and membranes by the clathrin adaptor complex (Keen, 1987). |
| GO:0035615 clathrin-cargo adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA clathrin-cargo adaptor activity from the AP-mu family node. Mu2 is the subunit that recognises YxxPhi tyrosine motifs in cargo tails; in the worm the FCHo study relies on this property, and dpy-23 mutants fail to internalise MIG-14 and accumulate corpses because CED-1 is not coupled to clathrin. Reason: This is the core molecular function of the mu2 subunit, conserved across the family and consistent with all worm loss-of-function data. Supporting Evidence: PMID:25303366 Tyrosine motifs comprised of YxxΞ¦, where x is any amino acid, and Ξ¦ is a large hydrophobic residue, bind the mu2 subunit of AP2 and are required for AP2-mediated internalization PMID:19047463 In particular, the ΞΌ2 subunit recruits cargo proteins containing the tyrosine-based YxxΟ motif (Owen and Evans, 1998) and mediates in part the association of the AP2 complex to membranes PMID:18160346 In dpy-23 mutants, MIG-14 accumulates at or near the plasma membrane. |
| GO:0045202 synapse | IDA PMID:19047463 Mu2 adaptin facilitates but is not essential for synaptic ve... | ACCEPT | Summary: GABA-neuron APM-2::GFP accumulates at synaptic varicosities with synaptobrevin and clathrin heavy chain, independent of AP180, synaptojanin, synaptotagmin or stonin. Reason: Directly demonstrated synaptic localisation where mu2 facilitates clathrin recruitment and synaptic vesicle recycling. Supporting Evidence: PMID:19047463 APM-2β·GFP is localized at synapses and colocalizes with the synaptic vesicle protein synaptobrevin/VAMP PMID:19047463 Interestingly, synaptic localization of APM-2β·GFP is not dependent on AP180 (unc-11), synaptojanin (unc-26), synaptotagmin (snt-1), or stonin (unc-41) (Fig. |
| GO:0050767 regulation of neurogenesis | IMP PMID:31259686 The Caenorhabditis elegans Tubby homolog dynamically modulat... | MODIFY | Summary: The cited study shows that dpy-23(e840) mutants have an expanded AWB ciliary membrane, a proximally shifted PI(4,5)P2 distribution in the AWB dendrite and enlarged TUB-1 occupancy at the ciliary base, and that TUB-1 localises the PPK-1 lipid kinase partly via DPY-23 at the periciliary membrane. Nothing in the paper concerns the generation of neurons. Reason: Regulation of neurogenesis (the generation of cells in the nervous system) does not describe the phenotype, which is remodelling of the sensory-cilium membrane of an existing neuron. The membrane-retrieval role of AP-2 at the ciliary base in setting ciliary membrane volume is better expressed as cilium organization. Proposed replacements: cilium organization Supporting Evidence: PMID:31259686 As in odr-1 mutants, loss of tub-1 fully suppressed the expanded ciliary membrane phenotype of dpy-23 mutants (Figure 7C) PMID:31259686 the distribution pattern of GFP::PLCΞ΄1-PH was shifted proximally in the AWB dendrite in dpy-23 mutants, in a pattern similar but not identical to the distribution observed in tub-1 mutants (Figure 7B). PMID:22342749 Disruption of endocytic gene function causes expansion of ciliary and/or periciliary membranes as well as defects in the ciliary targeting and/or transport dynamics of ciliary transmembrane and IFT proteins. |
| GO:0061357 positive regulation of Wnt protein secretion | IMP PMID:18160346 C. elegans AP-2 and retromer control Wnt signaling by regula... | KEEP AS NON CORE | Summary: dpy-23 mutants show the full set of EGL-20/Wnt-pathway phenotypes (HSN and Q-descendant migration, mab-5 activation, ALM/PLM polarity, V5 asymmetric division); DPY-23 acts in Wnt-producing cells, and MIG-14/Wntless accumulates at the plasma membrane in the mutants. AP-2-mediated internalisation of MIG-14 is required for its retromer-dependent retrieval and reuse, hence for Wnt secretion. Reason: Well-supported and specific, but Wnt secretion is a downstream physiological consequence of DPY-23's cargo-adaptor activity on MIG-14; the adaptor does not itself secrete Wnt. Retained as a non-core, context-specific process. Supporting Evidence: PMID:18160346 DPY-23 acts in Wnt-expressing cells to promote these processes. PMID:18160346 In dpy-23 mutants, MIG-14 accumulates at or near the plasma membrane. PMID:18160346 Based on our observations, we propose that intracellular trafficking of MIG-14 by AP-2 and retromer plays an important role in Wnt secretion. |
| GO:0070266 necroptotic process | IGI PMID:22157748 Endocytosis and intracellular trafficking contribute to necr... | UNDECIDED | Summary: IGI with the mec-4(d)-type necrosis model from a study reporting that endocytosis is required for the execution of necrotic neurodegeneration. Only the abstract is cached; it names dynamin, synaptotagmin and endophilin, not AP-2, so the specific dpy-23 experiment (presumably RNAi suppression of neurodegeneration) cannot be checked here. Reason: The claim is biologically plausible (AP-2-dependent endocytosis contributing to membrane loss during necrosis) but the cached record is abstract-only and does not mention dpy-23; the curator read the full text, so the annotation is neither accepted nor challenged. If confirmed it would be a non-core, indirect contribution rather than a core function. Supporting Evidence: PMID:22157748 Depletion of the key endocytic machinery components dynamin, synaptotagmin and endophilin suppresses necrotic neurodegeneration induced by diverse genetic and environmental insults in C. elegans. |
| GO:0072583 clathrin-dependent endocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: IBA clathrin-dependent endocytosis from node PTN000242371 (AP-2 mu clade), whose evidences include the worm gene itself. All worm loss-of-function data -- MIG-14 accumulation at the surface, synaptic clathrin mislocalisation and vesicle depletion, corpse accumulation, ciliary membrane expansion -- reflect impaired clathrin-mediated endocytosis. Reason: Core biological process of the AP-2 mu subunit; the appearance of dpy-23 among the node's sources reflects its own experimental support, not circularity. Supporting Evidence: file:worm/dpy-23/dpy-23-deep-research-falcon.md DPY-23/AP-2 facilitates clathrin-dependent synaptic-vesicle recycling but is not absolutely essential; residual AP-2 or alternative recycling routes likely remain. PMID:19047463 In apm-2 mutants, clathrin is mislocalized at synapses, and synaptic vesicle numbers and evoked responses are reduced to 60 and 65%, respectively. PMID:18160346 In dpy-23 mutants, MIG-14 accumulates at or near the plasma membrane. |
| GO:0072583 clathrin-dependent endocytosis | IMP PMID:25303366 The membrane-associated proteins FCHo and SGIP are allosteri... | ACCEPT | Summary: apm-2 mutants share the Dpy, Egl, Unc and 'jowls' phenotypes of the other AP-2 subunit mutants and of fcho-1; suppressor mutations in mu2 (interface residues and the phosphorylation site) restore AP-2 activity in fcho-1 nulls, and an endogenously tagged, protease-sensitive mu2 was used to show FCHo drives the open conformation of AP-2 in vivo. Reason: Genetic and biochemical evidence that DPY-23 is a functional subunit of the endocytic AP-2 complex whose conformational activation is required for clathrin-dependent endocytosis. Supporting Evidence: PMID:25303366 elegans (encoded by the apa-2 and apm-2 genes) result in animals with pleiotropic phenotypes including reduced body length (Dpy), egg-laying defects (Egl) and uncoordinated locomotion (Unc). PMID:25303366 A subsequent screen for bypass suppressors of fcho-1 nulls identified 71 compensatory mutations in all four AP2 subunits. PMID:25303366 Thus, these proteins stabilize nascent endocytic pits by exposing membrane and cargo binding sites on AP2. |
| GO:0097499 protein localization to non-motile cilium | IMP PMID:22342749 Endocytosis genes facilitate protein and membrane transport ... | KEEP AS NON CORE | Summary: Abstract-only in the cache, but the abstract itself states that AP-2 localises to the periciliary membrane compartment and that disrupting endocytic genes, including AP-2, causes expansion of ciliary/periciliary membranes and defects in ciliary targeting or transport of transmembrane and IFT proteins. Reason: Supported by the abstract, but the effect on ciliary protein distribution is a consequence of AP-2-mediated membrane retrieval at the ciliary base rather than DPY-23 transporting proteins into the cilium; kept as a non-core process. Supporting Evidence: PMID:22342749 Disruption of endocytic gene function causes expansion of ciliary and/or periciliary membranes as well as defects in the ciliary targeting and/or transport dynamics of ciliary transmembrane and IFT proteins. PMID:22342749 These data implicate C. elegans endocytosis proteins localized at the ciliary base in regulating ciliary and periciliary membrane volume |
| GO:0097499 protein localization to non-motile cilium | IMP PMID:31259686 The Caenorhabditis elegans Tubby homolog dynamically modulat... | KEEP AS NON CORE | Summary: In dpy-23(e840) AWB neurons the ciliary membrane is expanded, the PI(4,5)P2 reporter is shifted proximally in the dendrite, and TUB-1 occupies a larger area at the ciliary base, resembling the mislocalisation of ciliary proteins seen in other endocytic mutants. Reason: Genuine effect on the distribution of ciliary-base proteins, but indirect: DPY-23 retrieves membrane at the periciliary compartment and thereby shapes the domain in which TUB-1 and PPK-1 reside. Non-core. Supporting Evidence: PMID:31259686 Instead, this fusion protein occupied a larger area at the ciliary base in dpy-23 animals (Figure 7D), similar to the mislocalization phenotype of a subset of ciliary IFT and transmembrane proteins in endocytic mutants (Kaplan et al., 2012). PMID:31259686 TUB-1 acts in part via the DPY-23 AP-2 ΞΌ subunit to localize PPK-1 at the PCMC. |
| GO:1990075 periciliary membrane compartment | IDA PMID:22342749 Endocytosis genes facilitate protein and membrane transport ... | ACCEPT | Summary: AP-2 localises to a morphologically discrete periciliary membrane compartment at the base of sensory cilia (abstract), and DPY-23::GFP is enriched at the AWB and ASK periciliary membrane compartment in the later Tubby study. Reason: Directly observed and independently confirmed localisation at a site where AP-2-mediated membrane retrieval controls ciliary membrane volume. Supporting Evidence: PMID:22342749 Here we show that localization of the clathrin light chain, AP-2 clathrin adaptor, dynamin, and RAB-5 endocytic proteins overlaps with a morphologically discrete periciliary membrane compartment associated with sensory cilia. PMID:31259686 In wild-type animals, a DPY-23::GFP AP-2 ΞΌ2 subunit fusion protein was enriched at the PCMC of AWB in a domain similar to that occupied by TUB-1 |
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Download this section (compressed HTML)Q: Which cargo motifs does DPY-23 recognise in vivo, and does MIG-14 internalisation depend on a tyrosine-based signal read by mu2 or on the beta2/sigma2 dileucine site?
Q: Given that yolk uptake and synaptic vesicle recycling persist in apm-2 nulls, does the residual alpha/sigma2 hemicomplex support endocytosis on its own or do other adaptors (e.g. stonin/UNC-41, AP180/UNC-11) compensate?
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Download this section (compressed HTML)dpy-23 encodes an adaptin: specifically, it encodes an ortholog of the mu2 subunit of adaptor protein complex 2 (AP2); DPY-23 activity is required for receptor-mediated endocytosis and for normal body morphogenesis; DPY-23 also plays a key role in regulation of Wnt secretion by regulating trafficking of MIG-14/Wntless; when expressed in neurons, DPY-23 localizes to the synapse and co-localizes with SNB-1 at synaptic vesicles.
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