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- Cargo recognition for clathrin-mediated endocytosis
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
,