description
Recruitment of plasma membrane-localized cargo into clathrin-coated endocytic vesicles is mediated by interaction with a variety of clathrin-interacting proteins collectively called CLASPs (clathrin-associated sorting proteins). CLASP proteins, which may be monomeric or tetrameric, are recruited to the plasma membrane through interaction with phosphoinsitides and recognize linear or conformational sequences or post-translational modifications in the cytoplasmic tails of the cargo protein. Through bivalent interactions with clathrin and/or other CLASP proteins, they bridge the recruitment of the cargo to the emerging clathrin coated pit (reviewed in Traub and Bonifacino, 2013). The tetrameric AP-2 complex, first identified in early studies of clathrin-mediated endocytosis, was at one time thought to be the primary CLASP protein involved in cargo recognition at the plasma membrane, and indeed plays a key role in the endocytosis of cargo carrying dileucine- or tyrosine-based motifs. A number of studies have been performed to test whether AP-2 is essential for all forms of clathrin-mediated endocytosis (Keyel et al, 2006; Motely et al, 2003; Huang et al, 2004; Boucrot et al, 2010; Henne et al, 2010; Johannessen et al, 2006; Gu et al, 2013; reviewed in Traub, 2009; McMahon and Boucrot, 2011). Although depletion of AP-2 differentially affects the endocytosis of different cargo, extensive depletion of AP-2 through RNAi reduces clathrin-coated pit formation by 80-90%, and the CCPs that do form still contain AP-2, highlighting the critcical role of this complex in CME (Johannessen et al, 2006; Boucrot et al, 2010; Henne et al, 2010).In addition to AP-2, a wide range of other CLASPs including proteins of the beta-arrestin, stonin and epsin families, engage sorting motifs in other cargo and interact either with clathrin, AP-2 or each other to facilitate assembly of a clathin-coated pit (reviewed in Traub and Bonifacino, 2013)

external resources
NCBI:1427859
REACTOME:R-HSA-8856825
PUBMED:24186068
PUBMED:12952941
PUBMED:19696796
PUBMED:14985334
PUBMED:20448150
PUBMED:20485680
PUBMED:16382132
PUBMED:23482940
PUBMED:16870701

genes
ADRB2 , GRK2 , GRK3 , AP2A1 , AP2A2 , AP2B1 , AGTR1 , APOB , ARRB1 , ARRB2 , AVP , AVPR2 , CBL , CD3D , CD3G , CD4 , SCARB2 , CFTR , CHRM2 , AP2M1 , AP2S1 , CLTA , CLTB , CLTC , DAB2 , DVL2 , TOR1A , EGF , EGFR , EPS15 , GPS1 , GRB2 , AGFG1 , IGF2R , LDLR , LRP2 , M6PR , NEDD8 , RPS27A , ITSN1 , SH3GL1 , SH3GL2 , SH3GL3 , SLC18A3 , VAMP2 , VAMP7 , SYT1 , TACR1 , TF , TFRC , UBA52 , UBB , UBC , WNT5A , STAM , CLTCL1 , PICALM , FZD4 , COPS3 , VAMP8 , VAMP4 , HGS , REPS2 , COPS2 , VAMP3 , KIAA0319 , SNAP91 , STAM2 , TGOLN2 , COPS8 , COPS6 , COPS5 , STON1 , AAK1 , EPN2 , FCHO1 , SYT11 , NECAP1 , LDLRAP1 , TOR1B , EPN1 , UBQLN2 , UBQLN1 , SLC2A8 , SH3KBP1 , ITSN2 , COPS7A , COPS4 , NECAP2 , EPS15L1 , COPS7B , SGIP1 , REPS1 , STON2 , SYT8 , FCHO2 , SYT2 , SYT9 ,