Cargo recognition for clathrin-mediated endocytosis

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Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
23482940 AP2 hemicomplexes contribute independently to synaptic vesicle endocytosis

Hollopeter, G, Watanabe, S, Gu, M, Grant, BD, Sun, L, Jorgensen, EM, Liu, Q

Elife 2013
12952941 Clathrin-mediated endocytosis in AP-2-depleted cells

Bright, NA, Robinson, MS, Seaman, MN, Motley, A

J. Cell Biol. 2003
14985334 Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference

Huang, F, Sorkin, A, Marshall, W, Khvorova, A

J. Biol. Chem. 2004
16870701 A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors

Watkins, SC, Keyel, PA, Heuser, JE, Mishra, SK, Traub, LM, Roth, R

Mol. Biol. Cell 2006
16382132 Activation of the epidermal growth factor (EGF) receptor induces formation of EGF receptor- and Grb2-containing clathrin-coated pits

Johannessen, LE, Madshus, IH, Pedersen, NM, Stang, E, Pedersen, KW

Mol. Cell. Biol. 2006
24186068 Cargo recognition in clathrin-mediated endocytosis

Traub, LM, Bonifacino, JS

Cold Spring Harb Perspect Biol 2013
19696796 Tickets to ride: selecting cargo for clathrin-regulated internalization

Traub, LM

Nat. Rev. Mol. Cell Biol. 2009
20485680 Roles of AP-2 in clathrin-mediated endocytosis

Boucrot, E, Kirchhausen, T, Saffarian, S, Zhang, R

PLoS ONE 2010
20448150 FCHo proteins are nucleators of clathrin-mediated endocytosis

Boucrot, E, McMahon, HT, Meinecke, M, Henne, WM, Mittal, R, Vallis, Y, Evergren, E

Science 2010
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