unc-11 encodes the Caenorhabditis elegans orthologue of AP180 (PICALM/SNAP91 family), a monomeric clathrin assembly protein expressed at high levels throughout the nervous system and at lower levels in coelomocytes, vulval uv1 cells and intestine. Its conserved N-terminal ANTH domain binds phosphatidylinositol-4,5-bisphosphate on the cytoplasmic face of the presynaptic membrane and engages the R-SNARE synaptobrevin, while the divergent, disordered C-terminal assembly domain binds clathrin heavy chain, promotes clathrin lattice assembly and couples the coat to actin. Through these activities UNC-11 sorts synaptobrevin into regenerating synaptic vesicles and constrains the size of the budded vesicle: null mutants are viable but uncoordinated, synaptobrevin is mislocalised away from synaptic vesicles, membrane retrieval continues but vesicles are about 33% larger in diameter, and neurotransmitter release is greatly reduced. UNC-11 also mediates clathrin-dependent endocytosis of the postsynaptic AMPA-type glutamate receptor GLR-1, coupling ubiquitin-dependent receptor removal to synaptic strength.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000149 SNARE binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA SNARE binding from the AP180/CALM family node (human PICALM, rat AP180/CALM, plant and Dictyostelium members). In the worm, UNC-11 is required specifically to localise the R-SNARE synaptobrevin to synaptic vesicles while other vesicle proteins are targeted normally, matching the ANTH-domain VAMP-binding function of the family. Reason: Core molecular function: the ANTH domain captures synaptobrevin as cargo during vesicle regeneration, and the worm phenotype is the in vivo signature of that binding. Supporting Evidence: PMID:10397769 Furthermore, the UNC-11 protein is required to localize synaptobrevin, but not other synaptic vesicle proteins, to synaptic sites. PMID:10397769 We conclude that AP180 provides dual functions for the biogenesis of synaptic vesicles: to recruit synaptobrevin to synaptic vesicle membranes and to regulate vesicle diameter during clathrin assembly. |
| GO:0005515 protein binding | IPI PMID:14704431 A map of the interactome network of the metazoan C. elegans. | REMOVE | Summary: IPI with EYA-1 from the first-generation worm Y2H interactome map (abstract only). Reason: Generic protein binding from a high-throughput interactome screen carries no functional information and GO has no term for the accessory-protein contacts of AP180-family assembly domains; the functional content of the gene is carried by the clathrin-, phosphoinositide- and SNARE-binding rows. Removal does not dispute the reported interaction. Supporting Evidence: PMID:14704431 Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. |
| GO:0005515 protein binding | IPI PMID:19123269 Empirically controlled mapping of the Caenorhabditis elegans... | REMOVE | Summary: IPI with EYA-1 and ITSN-1 from an empirically controlled Y2H interactome mapping study; UNC-11 is not discussed in the cached text. Reason: Generic protein binding from a high-throughput interactome screen carries no functional information and GO has no term for the accessory-protein contacts of AP180-family assembly domains; the functional content of the gene is carried by the clathrin-, phosphoinositide- and SNARE-binding rows. Removal does not dispute the reported interaction. Supporting Evidence: PMID:19123269 Empirically controlled mapping of the Caenorhabditis elegans protein-protein |
| GO:0005515 protein binding | IPI PMID:19123269 Empirically controlled mapping of the Caenorhabditis elegans... | REMOVE | Summary: IPI with EYA-1 and ITSN-1 from an empirically controlled Y2H interactome mapping study; UNC-11 is not discussed in the cached text. Reason: Generic protein binding from a high-throughput interactome screen carries no functional information and GO has no term for the accessory-protein contacts of AP180-family assembly domains; the functional content of the gene is carried by the clathrin-, phosphoinositide- and SNARE-binding rows. Removal does not dispute the reported interaction. Supporting Evidence: PMID:19123269 Empirically controlled mapping of the Caenorhabditis elegans protein-protein |
| GO:0005515 protein binding | IPI PMID:19447967 Shifted Transversal Design smart-pooling for high coverage i... | REMOVE | Summary: IPI with SORB-1 and MAGU-1 from a smart-pooling Y2H methods study (abstract only). Reason: Generic protein binding from a high-throughput interactome screen carries no functional information and GO has no term for the accessory-protein contacts of AP180-family assembly domains; the functional content of the gene is carried by the clathrin-, phosphoinositide- and SNARE-binding rows. Removal does not dispute the reported interaction. Supporting Evidence: PMID:19447967 We employed two STD designs and two established methods to perform ORFeome-wide Y2H screens with 12 baits. |
| GO:0005515 protein binding | IPI PMID:19447967 Shifted Transversal Design smart-pooling for high coverage i... | REMOVE | Summary: IPI with SORB-1 and MAGU-1 from a smart-pooling Y2H methods study (abstract only). Reason: Generic protein binding from a high-throughput interactome screen carries no functional information and GO has no term for the accessory-protein contacts of AP180-family assembly domains; the functional content of the gene is carried by the clathrin-, phosphoinositide- and SNARE-binding rows. Removal does not dispute the reported interaction. Supporting Evidence: PMID:19447967 We employed two STD designs and two established methods to perform ORFeome-wide Y2H screens with 12 baits. |
| GO:0005515 protein binding | IPI PMID:23549480 SH3 interactome conserves general function over specific for... | REMOVE | Summary: IPI with SORB-1, MAGU-1 and ITSN-1 from the SH3-domain interactome study; the ITSN-1 SH3 contact is consistent with intersectin binding AP180-family proline/NPF motifs but is not further characterised for UNC-11 in the cached text. Reason: Generic protein binding from a high-throughput interactome screen carries no functional information and GO has no term for the accessory-protein contacts of AP180-family assembly domains; the functional content of the gene is carried by the clathrin-, phosphoinositide- and SNARE-binding rows. Removal does not dispute the reported interaction. Supporting Evidence: PMID:23549480 SH3 interactome conserves general function over specific form. |
| GO:0005515 protein binding | IPI PMID:23549480 SH3 interactome conserves general function over specific for... | REMOVE | Summary: IPI with SORB-1, MAGU-1 and ITSN-1 from the SH3-domain interactome study; the ITSN-1 SH3 contact is consistent with intersectin binding AP180-family proline/NPF motifs but is not further characterised for UNC-11 in the cached text. Reason: Generic protein binding from a high-throughput interactome screen carries no functional information and GO has no term for the accessory-protein contacts of AP180-family assembly domains; the functional content of the gene is carried by the clathrin-, phosphoinositide- and SNARE-binding rows. Removal does not dispute the reported interaction. Supporting Evidence: PMID:23549480 SH3 interactome conserves general function over specific form. |
| GO:0005515 protein binding | IPI PMID:23549480 SH3 interactome conserves general function over specific for... | REMOVE | Summary: IPI with SORB-1, MAGU-1 and ITSN-1 from the SH3-domain interactome study; the ITSN-1 SH3 contact is consistent with intersectin binding AP180-family proline/NPF motifs but is not further characterised for UNC-11 in the cached text. Reason: Generic protein binding from a high-throughput interactome screen carries no functional information and GO has no term for the accessory-protein contacts of AP180-family assembly domains; the functional content of the gene is carried by the clathrin-, phosphoinositide- and SNARE-binding rows. Removal does not dispute the reported interaction. Supporting Evidence: PMID:23549480 SH3 interactome conserves general function over specific form. |
| GO:0005543 phospholipid binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro ANTH-domain (IPR011417) mapping to phospholipid binding. The UNC-11 N-terminus carries the KKK phosphoinositide-binding motif shared with AP180, and worm protein binds PI(4,5)P2-containing liposomes in the deep-research literature. Reason: Correct, general parent of the phosphoinositide-binding rows. Supporting Evidence: PMID:10397769 both AP180 and UNC-11 share three adjacent lysine residues in this region. file:worm/unc-11/unc-11-deep-research-falcon.md Full-length protein associated with 50-nm liposomes containing 2% PIPβ and bridged them to F-actin, whereas phosphatidylcholine-only liposomes showed minimal association. |
| GO:0005545 1-phosphatidylinositol binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA 1-phosphatidylinositol binding from the family node (mouse and rat AP180). The ANTH domain of AP180 proteins binds phosphoinositides through a conserved lysine cluster present in UNC-11. Reason: Correct family-level lipid-binding function of the ANTH domain; the PI(4,5)P2-binding row is the more specific statement. Supporting Evidence: PMID:10397769 The conserved N-terminal domain of mammalian AP180 is known from biochemical studies to bind to inositol polyphosphates in vitro ( Norris et al. , 1995 ; Ye et al. , 1995 ; Hao et al. , 1997 ), and both AP180 and UNC-11 share three adjacent lysine residues in this region. |
| GO:0005545 1-phosphatidylinositol binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro AP180-like (IPR014712) mapping to 1-phosphatidylinositol binding. Reason: Correct family-level mapping. Supporting Evidence: PMID:10397769 both AP180 and UNC-11 share three adjacent lysine residues in this region. |
| GO:0005545 1-phosphatidylinositol binding | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse AP180 (O55012) for phosphoinositide binding; the KKK motif is conserved in UNC-11. Reason: Sound sequence-based transfer of the ANTH-domain lipid-binding property. Supporting Evidence: PMID:10397769 both AP180 and UNC-11 share three adjacent lysine residues in this region. |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA PI(4,5)P2 binding from the family node (rat AP180). PI(4,5)P2 recognition by the ANTH domain recruits AP180/CALM to the plasma membrane; deep-research literature reports worm UNC-11 binding PI(4,5)P2 liposomes. Reason: Core molecular function that positions UNC-11 at the presynaptic endocytic membrane. Supporting Evidence: PMID:10397769 This KKK motif is shared with the phosphoinositide-binding domain of the Ξ±-adaptin subunit ( Gaidarov et al. , 1996 ), and stretches of lysines have been shown to be required for the binding of inositol phosphates in arrestin file:worm/unc-11/unc-11-deep-research-falcon.md Full-length protein associated with 50-nm liposomes containing 2% PIPβ and bridged them to F-actin, whereas phosphatidylcholine-only liposomes showed minimal association. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to Golgi apparatus, derived from the 1999 report of UNC-11 colocalising with clathrin in the Golgi area of cell bodies. The cached full text describes cell-body staining but the functional site is the presynaptic membrane. Reason: Localisation is recorded by UniProt from the primary paper and CALM-family proteins do act at Golgi/endosomal clathrin sites, but it is not the core site of UNC-11 activity. Supporting Evidence: file:worm/unc-11/unc-11-uniprot.txt Note=Colocalized with clathrin in the Golgi area. PMID:10397769 In neurons, UNC-11 is enriched at presynaptic terminals but is also present in cell bodies. |
| GO:0005905 clathrin-coated pit | IBA GO_REF:0000033 | ACCEPT | Summary: IBA clathrin-coated pit from the family node (fly LAP, mouse Picalm, human PICALM and the worm gene itself). UNC-11 is the AP180 assembly protein that nucleates clathrin lattices at presynaptic coated pits. Reason: Core location, supported by family data and by the worm IDA on which the node partly rests. Supporting Evidence: PMID:10397769 Endocytosis of membranes through clathrin-coated pits is initiated when clathrin is recruited and organized into lattices by the heterotetrameric adaptor protein AP-2 and the monomeric adaptor protein AP180 (for review see Schmid, 1997 ). file:worm/unc-11/unc-11-uniprot.txt SUBCELLULAR LOCATION: Membrane, clathrin-coated pit |
| GO:0005905 clathrin-coated pit | IDA PMID:10397769 UNC-11, a Caenorhabditis elegans AP180 homologue, regulates ... | ACCEPT | Summary: UniProt records clathrin-coated pit localisation from this paper; the cached text documents enrichment at presynaptic sites and the AP180 coated-pit assembly role, and the coated-pit assignment reflects the paper's immunolocalisation and clathrin-assembly data. Reason: Consistent with the enrichment at presynaptic terminals and with the clathrin-assembly function; accepted, deferring to the curator for the exact figure. Supporting Evidence: PMID:10397769 In neurons, UNC-11 is enriched at presynaptic terminals but is also present in cell bodies. file:worm/unc-11/unc-11-uniprot.txt SUBCELLULAR LOCATION: Membrane, clathrin-coated pit |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/UniProt mapping to clathrin-coated pit. Reason: Correct core location. Supporting Evidence: file:worm/unc-11/unc-11-uniprot.txt SUBCELLULAR LOCATION: Membrane, clathrin-coated pit |
| GO:0006511 ubiquitin-dependent protein catabolic process | IMP PMID:12123612 Ubiquitin and AP180 regulate the abundance of GLR-1 glutamat... | MARK AS OVER ANNOTATED | Summary: Abstract-only: ubiquitin overexpression lowers GLR-1 abundance at synapses and this requires unc-11. UNC-11 performs the clathrin-dependent internalisation of ubiquitinated GLR-1; whether the receptor is then degraded, and whether UNC-11 contributes to that degradation, is not shown. Reason: UNC-11 executes the endocytic removal step that ubiquitination triggers, so the annotation is not wrong, but 'ubiquitin-dependent protein catabolic process' asserts participation in proteolytic breakdown that the evidence does not establish; the receptor-abundance regulation row from the same paper captures the finding better. Supporting Evidence: PMID:12123612 overexpression of ubiquitin decreased the abundance of GLR-1 at synapses and decreased the density of GLR-1-containing synapses, and these effects were prevented by mutations in the unc-11 gene, which encodes a clathrin adaptin protein (AP180). |
| GO:0006898 receptor-mediated endocytosis | IDA PMID:10397769 UNC-11, a Caenorhabditis elegans AP180 homologue, regulates ... | ACCEPT | Summary: Receptor-mediated endocytosis assigned from the AP180 characterisation paper. The cached text shows UNC-11 is a clathrin assembly protein at presynaptic terminals and that endocytosis persists but yields enlarged vesicles in mutants; later work shows UNC-11 is required for clathrin-dependent endocytosis of the GLR-1 receptor. Reason: Biologically correct: UNC-11 is a clathrin-coated-pit assembly protein that internalises membrane receptors such as GLR-1. The specific assay behind the 1999 IDA is not visible in the cached text, so the later GLR-1 evidence is cited in support. Supporting Evidence: PMID:10397769 Endocytosis of membranes through clathrin-coated pits is initiated when clathrin is recruited and organized into lattices by the heterotetrameric adaptor protein AP-2 and the monomeric adaptor protein AP180 (for review see Schmid, 1997 ). PMID:22213799 GLR-1 AMPARs undergo activity-dependent endocytosis in a process that requires UNC-11/AP180 (Fig. |
| GO:0006898 receptor-mediated endocytosis | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping to receptor-mediated endocytosis. Reason: Correct; GLR-1 endocytosis requires UNC-11. Supporting Evidence: PMID:22213799 GLR-1 AMPARs undergo activity-dependent endocytosis in a process that requires UNC-11/AP180 (Fig. |
| GO:0006900 vesicle budding from membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA vesicle budding from membrane from the family node (human PICALM). UNC-11 regulates the diameter of the budded vesicle during clathrin assembly; null mutants make 33% larger synaptic vesicles. Reason: Core process: AP180 shapes the budding clathrin-coated vesicle and sets its size. Supporting Evidence: PMID:10397769 In the two null mutants, mean vesicle diameter was 33% larger ( unc-11(e47) 39.1 Β± 7.3 nm; unc-11(q358) 40.4 Β± 8.0 nm). PMID:10397769 We conclude that AP180 provides dual functions for the biogenesis of synaptic vesicles: to recruit synaptobrevin to synaptic vesicle membranes and to regulate vesicle diameter during clathrin assembly. |
| GO:0008021 synaptic vesicle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA synaptic vesicle from the AP180 node PTN001119474 (rat AP180/CALM). AP180 associates with clathrin-coated synaptic vesicle intermediates and with synaptobrevin on the vesicle, but its activity is exercised at the presynaptic endocytic-zone membrane. Reason: Genuine association with the coated intermediates of the synaptic vesicle pool; retained as a non-core location because the extrinsic presynaptic endocytic zone membrane row states the functional site. Supporting Evidence: PMID:10397769 In neurons, UNC-11 is enriched at presynaptic terminals but is also present in cell bodies. PMID:10397769 Furthermore, the UNC-11 protein is required to localize synaptobrevin, but not other synaptic vesicle proteins, to synaptic sites. |
| GO:0009791 post-embryonic development | IMP PMID:10397769 UNC-11, a Caenorhabditis elegans AP180 homologue, regulates ... | MARK AS OVER ANNOTATED | Summary: unc-11 null mutants are viable and develop normally; the only developmental arrest reported is a synthetic L1 arrest of unc-11; snb-1 hypomorph double mutants that mimics snb-1 null. Reason: The phenotype is synthetic and reflects loss of residual synaptobrevin function rather than a role of UNC-11 in post-embryonic development; over-annotation of a synaptic-transmission requirement. Supporting Evidence: PMID:10397769 In fact, the double mutants unc-11(e47); snb-1(md247) and unc-11(n2954) ; snb-1(md247) arrest development in the first larval stage similar to snb-1(js124) null mutants. PMID:10397769 We demonstrate that mutants homozygous for null alleles of unc-11 are viable, but are defective for the relea |
| GO:0030136 clathrin-coated vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: IBA clathrin-coated vesicle from the family node (plant, Dictyostelium, rat and human members). AP180 remains on the budded clathrin-coated vesicle whose size it sets. Reason: Core location for a clathrin assembly protein; consistent with UniProt and the vesicle-size phenotype. Supporting Evidence: file:worm/unc-11/unc-11-uniprot.txt Cytoplasmic vesicle, clathrin-coated PMID:10397769 Finally, in unc-11 mutants, synaptic membrane still undergoes endocytosis but vesicle diameter is significantly larger. |
| GO:0030136 clathrin-coated vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/UniProt mapping to clathrin-coated vesicle. Reason: Correct. Supporting Evidence: file:worm/unc-11/unc-11-uniprot.txt Cytoplasmic vesicle, clathrin-coated |
| GO:0030276 clathrin binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro AP180-like mapping to clathrin binding; the UNC-11 C-terminal region promotes clathrin assembly in vitro. Reason: Core molecular function of the assembly domain. Supporting Evidence: PMID:10397769 Likewise, the C-terminal region of UNC-11 promotes clathrin assembly in vitro despite minimal sequence similarity with AP180 (Golan, Prasad, Lafer, and Alfonso, unpublished data). |
| GO:0030276 clathrin binding | ISS PMID:10397769 UNC-11, a Caenorhabditis elegans AP180 homologue, regulates ... | ACCEPT | Summary: ISS clathrin binding from the characterisation paper, based on homology to AP180 whose C-terminus binds clathrin and on the reported in vitro clathrin-assembly activity of the UNC-11 C-terminal region. Reason: Well-founded inference; clathrin binding is the defining biochemical property of AP180 assembly proteins. Supporting Evidence: PMID:10397769 The C-terminal domain of the mouse AP180 molecule interacts with clathrin and by itself can promote the assembly of clathrin cages ( Ye and Lafer, 1995b ). PMID:10397769 Likewise, the C-terminal region of UNC-11 promotes clathrin assembly in vitro despite minimal sequence similarity with AP180 (Golan, Prasad, Lafer, and Alfonso, unpublished data). |
| GO:0032050 clathrin heavy chain binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA clathrin heavy chain binding from the family node (mouse/rat AP180, human PICALM). AP180 assembly domains bind the clathrin heavy chain terminal domain through clathrin-box and DLL motifs and drive lattice assembly. Reason: Core molecular function, consistent with the in vitro assembly activity of the UNC-11 C-terminus. Supporting Evidence: PMID:10397769 Likewise, the C-terminal region of UNC-11 promotes clathrin assembly in vitro despite minimal sequence similarity with AP180 (Golan, Prasad, Lafer, and Alfonso, unpublished data). |
| GO:0040011 locomotion | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA mapping to locomotion, reflecting the Unc phenotype. Reason: The uncoordinated phenotype is an organismal consequence of defective synaptic vesicle recycling, not a process the protein executes. Supporting Evidence: PMID:10397769 Mutations in unc-11 were first identified by Brenner (1974) based on their uncoordinated locomotory phenotype: the mutant animals coil and jerk, particularly when going backward. |
| GO:0040011 locomotion | IMP PMID:10397769 UNC-11, a Caenorhabditis elegans AP180 homologue, regulates ... | KEEP AS NON CORE | Summary: unc-11 mutants coil and jerk, especially when backing; the defect is rescued by cosmid C32E8. Reason: Robust but downstream organismal phenotype of impaired neurotransmission; non-core. Supporting Evidence: PMID:10397769 Mutations in unc-11 were first identified by Brenner (1974) based on their uncoordinated locomotory phenotype: the mutant animals coil and jerk, particularly when going backward. PMID:10397769 unc-11 maps genetically between the fog-1 and dpy-5 loci on chromosome I, and a cosmid contained within this interval, C32E8, rescued the unc-11 locomotion phenotype (Figure 1 ). |
| GO:0042734 presynaptic membrane | IDA PMID:10397769 UNC-11, a Caenorhabditis elegans AP180 homologue, regulates ... | ACCEPT | Summary: Antibody staining shows UNC-11 enriched at presynaptic terminals (nerve ring and nerve cords, overlapping synaptotagmin-positive regions) and retained in the neuropil when synaptic vesicles are trapped in cell bodies in unc-104 mutants. Reason: Directly demonstrated presynaptic localisation at the membrane where clathrin-mediated retrieval occurs. Supporting Evidence: PMID:10397769 In neurons, UNC-11 is enriched at presynaptic terminals but is also present in cell bodies. PMID:10397769 By contrast, UNC-11 protein remains abundant in the neuropil (Figure 5 D). |
| GO:0048268 clathrin coat assembly | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to clathrin coat assembly. UNC-11's C-terminus promotes clathrin assembly in vitro and the protein sets vesicle size during clathrin assembly in vivo. Reason: Core process of an AP180 assembly protein. Supporting Evidence: PMID:10397769 Likewise, the C-terminal region of UNC-11 promotes clathrin assembly in vitro despite minimal sequence similarity with AP180 (Golan, Prasad, Lafer, and Alfonso, unpublished data). PMID:10397769 We conclude that AP180 provides dual functions for the biogenesis of synaptic vesicles: to recruit synaptobrevin to synaptic vesicle membranes and to regulate vesicle diameter during clathrin assembly. |
| GO:0048488 synaptic vesicle endocytosis | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping to synaptic vesicle endocytosis. Reason: Correct core process: UNC-11 regenerates correctly sized, synaptobrevin-containing vesicles from the presynaptic membrane. Supporting Evidence: PMID:10397769 Finally, in unc-11 mutants, synaptic membrane still undergoes endocytosis but vesicle diameter is significantly larger. |
| GO:0048488 synaptic vesicle endocytosis | IMP PMID:10397769 UNC-11, a Caenorhabditis elegans AP180 homologue, regulates ... | ACCEPT | Summary: In unc-11 nulls synaptic membrane is still retrieved, but vesicles are 33% larger and lack normal synaptobrevin content, and evoked release is reduced; AP180 therefore acts in the endocytic regeneration of synaptic vesicles, setting size and cargo composition, without being essential for membrane internalisation itself. Reason: Direct participation in synaptic vesicle endocytosis (coat assembly, cargo capture, vesicle-size control), even though other retrieval routes persist. Supporting Evidence: PMID:10397769 Finally, in unc-11 mutants, synaptic membrane still undergoes endocytosis but vesicle diameter is significantly larger. PMID:10397769 In the two null mutants, mean vesicle diameter was 33% larger ( unc-11(e47) 39.1 Β± 7.3 nm; unc-11(q358) 40.4 Β± 8.0 nm). file:worm/unc-11/unc-11-deep-research-falcon.md Null alleles produced evoked EPSCs of **0.19β0.20 nA** versus **3.24 Β± 0.20 nA** in wild type and miniature frequencies of **6β11 Hz** versus **53 Β± 3 Hz**, while amplitudes rose to **30β31 pA** from **22 Β± 2 pA**. |
| 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 an abstract-only study reporting that endocytosis is required for necrotic neurodegeneration; the abstract names dynamin, synaptotagmin and endophilin, not unc-11. Reason: Plausible (AP180-dependent endocytosis contributing to membrane loss during necrosis) but not verifiable from the cached abstract; neither accepted nor challenged. If confirmed it would be a non-core, indirect contribution. 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 the family node (plant, fly, mouse, rat and human AP180/CALM proteins). UNC-11 assembles clathrin coats at presynaptic membranes and is required for GLR-1 endocytosis. Reason: Core process. Supporting Evidence: PMID:22213799 GLR-1 AMPARs undergo activity-dependent endocytosis in a process that requires UNC-11/AP180 (Fig. PMID:10397769 Finally, in unc-11 mutants, synaptic membrane still undergoes endocytosis but vesicle diameter is significantly larger. |
| GO:0072583 clathrin-dependent endocytosis | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping to clathrin-dependent endocytosis. Reason: Correct core process. Supporting Evidence: PMID:22213799 GLR-1 AMPARs undergo activity-dependent endocytosis in a process that requires UNC-11/AP180 (Fig. |
| GO:0098894 extrinsic component of presynaptic endocytic zone membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA extrinsic component of presynaptic endocytic zone membrane from the AP180 node (rat AP180/CALM). UNC-11 is enriched at presynaptic terminals where, as a peripheral PI(4,5)P2-binding protein, it assembles clathrin for vesicle retrieval. Reason: The most precise statement of UNC-11's functional site, consistent with the worm immunolocalisation and with the ANTH lipid-binding mechanism. Supporting Evidence: PMID:10397769 In neurons, UNC-11 is enriched at presynaptic terminals but is also present in cell bodies. file:worm/unc-11/unc-11-deep-research-falcon.md Full-length protein associated with 50-nm liposomes containing 2% PIPβ and bridged them to F-actin, whereas phosphatidylcholine-only liposomes showed minimal association. |
| GO:1902683 regulation of receptor localization to synapse | IDA PMID:12123612 Ubiquitin and AP180 regulate the abundance of GLR-1 glutamat... | KEEP AS NON CORE | Summary: Abstract-only: ubiquitin-driven loss of GLR-1 from synapses and of GLR-1-containing synapses is prevented by unc-11 mutations, i.e. UNC-11-dependent endocytosis removes ubiquitinated GLR-1 from postsynaptic elements. Reason: Supported by the abstract and by later full-text work showing GLR-1 endocytosis requires UNC-11; a genuine but cargo-specific, regulatory consequence of the core endocytic function, so non-core. Supporting Evidence: PMID:12123612 overexpression of ubiquitin decreased the abundance of GLR-1 at synapses and decreased the density of GLR-1-containing synapses, and these effects were prevented by mutations in the unc-11 gene, which encodes a clathrin adaptin protein (AP180). PMID:22213799 GLR-1 AMPARs undergo activity-dependent endocytosis in a process that requires UNC-11/AP180 (Fig. |
| GO:1903539 protein localization to postsynaptic membrane | IMP PMID:22213799 RAB-6.2 and the retromer regulate glutamate receptor recycli... | MODIFY | Summary: unc-11 mutations prevent the loss of GLR-1::GFP puncta caused by rab-6.2 or activated RAB-6.2, because UNC-11 mediates the endocytosis that removes GLR-1 from the postsynaptic membrane. The gene product thus controls GLR-1 removal, not its delivery to the postsynaptic membrane. Reason: 'Protein localization to postsynaptic membrane' misstates the direction of the effect: UNC-11 internalises GLR-1, and its loss increases surface receptor. The regulatory term already used for the same cargo in the ubiquitin study describes the finding accurately. Proposed replacements: regulation of receptor localization to synapse Supporting Evidence: PMID:22213799 GLR-1 AMPARs undergo activity-dependent endocytosis in a process that requires UNC-11/AP180 (Fig. PMID:22213799 We analyzed GLR-1::GFP localization in rab-6.2; unc-11 double mutants and found that mutations in unc-11 prevent the decrease in GLR-1::GFP puncta number and fluorescence intensity observed in rab-6.2 mutants (Fig. |
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