apa-2 (apt-4) — AP-2 complex subunit alpha (Q22601, TrEMBL) — curation notes

Identity

apa-2 (T20B5.1; older alias apt-4) encodes the alpha-adaptin large subunit of the AP-2 clathrin adaptor complex PMID:23482940. Two likely-null alleles exist: b1044 (925 bp deletion in the trunk) and ox422 (Lys215 premature stop); neither produces full-length protein PMID:23482940.
APA-2::GFP is expressed in most cells and is highest in the nervous system PMID:23482940.

Alpha-adaptin forms a hemicomplex with sigma2; the alpha/sigma2 half remains localised and partially functional without mu2, and the alpha appendage ("ear") recruits accessory endocytic proteins such as dynamin, AP180, epsin and eps15 PMID:23482940 PMID:10588660.
Cargo specificity: recovery of di-leucine cargo depends on alpha more than mu2, whereas MIG-14/Wntless (tyrosine motif) depends on mu2 PMID:23482940 PMID:23482940.
Accessory-protein interactions documented in the worm (all via the alpha subunit): RME-6 (Vps9-domain RAB-5 GEF) co-immunoprecipitates with alpha-adaptin and carries a WxxF alpha-ear motif PMID:15895077; RME-4 (DENN protein, RAB-35 GEF) binds AP-2 (abstract) PMID:18354496; DAB-1 binds clathrin and APT-4 in vitro (abstract) PMID:16497226; CED-1 intracellular domain and CED-6 bind APA-2 directly and co-IP in vivo PMID:23696751.

Coelomocytes: mRFP::alpha-adaptin marks plasma-membrane clathrin-coated pits together with CHC-1, unevenly distributed around the plasma membrane PMID:15895077 PMID:15895077.
Synapses: APT-4::GFP is predominantly at synaptic puncta and behaves as a periactive-zone / endocytic-intermediate marker whose abundance rises in synaptojanin and endophilin mutants PMID:19043554 PMID:22588719. Tagged alpha-adaptin remains at synapses and the coelomocyte plasma membrane in mu2 mutants PMID:23482940.
Phagosomes: APA-2::GFP surrounds apoptotic germ-cell corpses in a CED-1/CED-6- and clathrin-dependent manner PMID:23696751.

Yolk endocytosis: alpha-adaptin RNAi abolishes YP170::GFP uptake, and embryos from such mothers die PMID:10588660 PMID:10588660. However, apa-2 null mutants are viable with near-normal embryonic viability (2.4% vs 1.1% lethality) and still endocytose yolk, so AP-2 assists DAB-1 rather than being absolutely required PMID:23482940 PMID:23482940.
Synaptic vesicle endocytosis: loss of alpha alone reduces synaptic vesicle number ~30% and evoked amplitude ~25–42%; complete loss of AP-2 (alpha + mu2) reduces vesicles 70% and produces large vacuoles PMID:23482940 PMID:23482940.
Whole-animal phenotypes: variable dumpy (rescued by neuronal expression), jowls, Egl, mildly Unc; apa-2 apm-2 double mutants are almost fully embryonic lethal PMID:23482940 PMID:23482940. apa-2 mutants share the jowls phenotype with fcho-1, and fcho-1 bypass suppressors include mutations in the alpha solenoid PMID:25303366.
Apoptotic cell clearance: apa-2 RNAi increases germ-cell corpses; APA-2::GFP rescues PMID:23696751.
DAB-1 localisation in oocytes depends on clathrin and AP-2 (abstract only) PMID:17636000.

GO:0032794 "GTPase activating protein binding" (IPI with RME-6): RME-6 is a Vps9-domain RAB-5 guanine-nucleotide exchange factor, not a GAP, and GO has no GEF-binding term; the row is removed as mislabelled (the interaction itself stands and is recorded above).
GO:0009792 embryo development (IMP, alpha RNAi): contradicted by viable apa-2 null strains with near wild-type embryonic viability; the RNAi lethality most likely reflects yolk deprivation of oocytes. Removed.
Four generic protein-binding rows (RME-6, DAB-1, RME-4, CED-6) are removed as uninformative per project policy; the interactions are genuine alpha-appendage/accessory-protein contacts.

Quantified dileucine-cargo defect: an intestinal eGFP-CD4 ExxxLL reporter accumulates ~7-fold at the basolateral membrane in apa-2(ox422) [file:worm/apa-2/apa-2-deep-research-falcon.md "An intestinal eGFP–CD4 reporter carrying an ExxxLL signal accumulated at the basolateral membrane in apa-2(ox422) animals, with fluorescence of 14,907 ± 990 versus 1,998 ± 275 in wild type (p<0.0001)."].
AP-2 subunit mutants (apa-2, apm-2, aps-2) reduce GLR-1 glutamate receptor abundance at ventral-cord synapses via an early secretory/endosomal step (Garafalo et al. 2015, DOI 10.1091/mbc.e14-06-1048).
NCAP-1/NECAP antagonises FCHO-1 by recognising open, phosphorylated AP-2 (Beacham et al. 2018); APA-2::GFP was the reporter for complex dynamics.
CED-1's intracellular domain binds APA-2 but not the other AP-2 subunits tested, making alpha the physical bridge to the phagocytic receptor [file:worm/apa-2/apa-2-deep-research-falcon.md "The intracellular region of CED-1 binds APA-2 in vitro, whereas the other tested AP-2 subunits did not detectably bind CED-1."].