9.B.278.1.4
AP2 clathrin adaptor complex, AP2A1, A2, B1, M1, S1.  Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways and are vesicle coat components that appear to be involved in cargo selection and vesicle formation (Nakatsu and Ohno 2003). AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome (Owen et al. 2004). The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components; AP2 directly regulates PAR1 trafficking, (Paing et al. 2006). Clathrin-associated adaptor protein (AP) complexes, which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes, are considered to be the major clathrin adaptors contributing to CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis and seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway (Lau and Chou 2008). During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (Marcello et al. 2013). The AP-2 mu subunit binds to transmembrane cargo proteins and recognizes the Y-X-X-Phi motifs. The surface region interacting with the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2 (Partlow et al. 2019). Subunits α1, α2 and β appear to be homologous.