dpy-23 (apm-2) — AP-2 complex subunit mu (P35603) — curation notes

Identity

• dpy-23 (also apm-2, ORF R160.1) encodes the only mu2 (AP50) subunit of the AP-2 clathrin adaptor complex in C. elegans PMID:19047463.
• Two loss-of-function alleles: e840 (≈100 kb deletion removing the whole coding sequence plus 17 neighbouring ORFs) and gm17 (splice-donor point mutation in the last intron) PMID:19047463.
• Mutants are dumpy, slightly uncoordinated and egg-laying defective, and all three defects are rescued by a 12 kb genomic fragment PMID:19047463.

Complex membership and molecular activity

• Mu2 is the cargo-recognition subunit of AP-2: it binds tyrosine-based YxxΦ sorting motifs and contributes to membrane (PI(4,5)P2) association PMID:19047463 PMID:25303366.
• Loss of mu2 destabilises the complex: alpha-adaptin (APA-2) is reduced to 60% (e840) and 12% (gm17), but residual alpha remains bound to sigma2 and still localises to coelomocyte plasma membrane and synapses PMID:19047463.
• In the FCHo/SGIP allosteric-activation study, apm-2 mutants phenocopy the other AP-2 subunit mutants (Dpy, Egl, Unc, "jowls"); bypass suppressors of fcho-1 map to all four AP-2 subunits, including residues at the mu2 interface and the mu2 phosphorylation site, and an HA/TEV-tagged endogenous mu2 was used to show that FCHo promotes the open, protease-sensitive conformation of AP-2 in vivo PMID:25303366 PMID:25303366.

Endocytic roles

• Synapse: APM-2::GFP is expressed in virtually all tissues; in GABA neurons it localises to synapses, colocalising with synaptobrevin and clathrin heavy chain PMID:19047463 PMID:19047463. In apm-2 mutants clathrin is mislocalised at synapses and synaptic vesicle number and evoked responses fall to ~60–65% of wild type, but synaptic vesicles are still recycled; mu2 therefore facilitates but is not essential for synaptic vesicle recycling PMID:19047463 PMID:19047463.
• Oocyte yolk uptake: mu2 RNAi did not reduce YP170::GFP uptake, unlike chc-1, apa-2 and apb-1 RNAi PMID:10588660, and >98% of apm-2 null gonads still take up yolk, so mu2 is less important than alpha/beta2 for yolk endocytosis PMID:19047463. RNAi of mu2 produces severely Dpy progeny PMID:10588660.
• Wnt secretion: dpy-23 mutants show Wnt-like phenotypes (HSN and Q-descendant migration, ALM/PLM polarity, asymmetric division); DPY-23 acts in EGL-20/Wnt-producing hypodermal cells, and the Wntless orthologue MIG-14 accumulates at or near the plasma membrane in dpy-23 mutants, indicating AP-2-dependent endocytosis of MIG-14 is required for its retromer-mediated retrieval and hence Wnt secretion PMID:18160346 PMID:18160346 PMID:18160346.
• Apoptotic-cell clearance: RNAi of apa-2, apb-1 or dpy-23 increases germ-cell corpses in the same genetic pathway as ced-1/ced-6; DPY-23::GFP surrounds corpses, and DPY-23 binds CED-6, DYN-1 and LST-4 directly in GST pull-downs and co-IPs with CED-6 and LST-4 in vivo PMID:23696751 PMID:23696751.
• Sensory cilia: DPY-23::GFP is enriched at the periciliary membrane compartment (PCMC) of AWB PMID:31259686; AP-2 mutants show expanded ciliary/periciliary membranes and ciliary protein mislocalisation (abstract only) PMID:22342749. In dpy-23(e840) the PI(4,5)P2 reporter is shifted proximally in the AWB dendrite and TUB-1 occupies a larger area at the ciliary base; tub-1 loss suppresses the expanded AWB ciliary membrane of dpy-23 PMID:31259686.
• Necrosis: the necroptosis IGI (PMID:22157748) is abstract-only in the cache; the abstract names dynamin, synaptotagmin and endophilin but not AP-2, so dpy-23's contribution cannot be verified here.

Curation decisions (summary)

• Core: clathrin-cargo adaptor activity within the AP-2 adaptor complex at the plasma membrane; clathrin-dependent / receptor-mediated endocytosis (MIG-14, CED-1 phagocytic receptor, synaptic vesicle proteins); presynaptic and periciliary membrane localisation.
• Non-core / downstream: body morphogenesis, positive regulation of Wnt secretion, protein localisation to cilium.
• Over-propagated: GO:0006896 Golgi to vacuole transport comes from a deep AP-mu family node whose experimental seeds are AP-1/AP-3/AP-4 mu subunits; AP-2 mu acts at the plasma membrane, so this is removed.
• GO:0050767 regulation of neurogenesis (PMID:31259686) does not describe the cilia-membrane phenotype; proposed replacement GO:0044782 cilium organization.

Additional literature surfaced by deep research (not in GOA; see dpy-23-deep-research-falcon.md)

• apm-2 mutants reduce GLR-1::GFP in ventral-cord puncta by ~26–30% with receptor accumulating in cell-body endosomes, implying AP-2 also supports a secretory/endosomal delivery step for GLR-1 (Garafalo et al. 2015, DOI 10.1091/mbc.e14-06-1048) [file:worm/dpy-23/dpy-23-deep-research-falcon.md "Two independent apm-2 alleles reduced GLR-1::GFP fluorescence in ventral-nerve-cord puncta by 26% and 30%, respectively"].
• Reduction-of-function dpy-23 alleles (S434T, Y275D, null) suppress nekl-2; nekl-3 developmental arrest (Joseph et al. 2020, DOI 10.1371/journal.pgen.1008633) [file:worm/dpy-23/dpy-23-deep-research-falcon.md "The DPY-23 S434T allele fd155 allowed 98% of otherwise severely affected nekl-2; nekl-3 animals to reach adulthood"].
• SEL-5/AAK1 phosphorylates DPY-23 T160 (≈ mammalian AP2M1 T156), but the phospho-site is dispensable for the Wnt-dependent phenotypes examined (Knop et al. 2024, DOI 10.7554/eLife.91054) [file:worm/dpy-23/dpy-23-deep-research-falcon.md "SEL-5 loss reduced phosphorylation of DPY-23 at T160, corresponding to mammalian AP2M1 T156, but did not eliminate it"].