AP-2 directly binds some endocytic cargo

Stable Identifier
R-HSA-8866277
Type
Reaction [binding]
Species
Homo sapiens
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AP-2 is a heterotetrameric complex that was originally identified as a factor required to help assemble clathrin at the plasma membrane to promote endocytosis (Keen et al, 1987; reviewed in Robinson, 2015). In addition to its structural role, AP-2 also contributes to cargo recognition and recruitment through direct binding of tyrosine- and dileucine-based sorting motifs in the cytoplasmic tails of cargo such as the transferrin receptor, cation dependent and independent mannose-6-phosphate receptors, CFTR, CD3 and CD4 proteins, glucose transporters and the viral Nef protein, among many others (Collawn et al, 1990; Jadot et al, 1992; Storch and Braulke, 2001; Ohno et al, 1995; Letourneur and Klausner, 1992; Kelly et al, 2008; Schmidt et al, 2006; Doray et al, 2007; Chaudhuri et al, 2007; Lindwasser et al, 2008; Collaco et al, 2010; Fu et al, 2012; reviewed in Traub and Bonifacino, 2013). Both membrane recruitment and interaction of AP-2 with the sorting signals of cargo are mediated by the large 'trunk' domain of AP-2, made up of the medium and small subunits and the N-terminal domains of the 2 large subunits (Collins et al, 2002; Heuser and Keen, 1988; Owen and Evans, 1998; Kelly et al, 2008; reviewed in Traub and Bonifacino, 2013).

AP-2 also facilitates the recruitment of many other endocytic cargo indirectly by binding to CLASP proteins (clathrin associated sorting proteins) that themselves interact with cargo (Schmid et al, 2006; Edeling et al, 2006; reviewed in Traub and Bonifacino, 2013). CLASP proteins generally interact with AP-2 through the globular 'beta-2 ear', one of 2 ear domains made up of the C-terminal regions of the two large subunits (reviewed in Owen, 2004; Schmid and McMahon, 2007).

Literature References
PubMed ID Title Journal Year
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Fu, L, Rab, A, Tang, LP, Rowe, SM, Bebok, Z, Collawn, JF

Biochem. J. 2012
16723738 Endocytosis of the glucose transporter GLUT8 is mediated by interaction of a dileucine motif with the beta2-adaptin subunit of the AP-2 adaptor complex

Schmidt, U, Briese, S, Leicht, K, Schürmann, A, Joost, HG, Al-Hasani, H

J. Cell. Sci. 2006
18032517 A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2

Lindwasser, OW, Smith, WJ, Chaudhuri, R, Yang, P, Hurley, JH, Bonifacino, JS

J. Virol. 2008
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J. Biol. Chem. 1992
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Robinson, MS

Traffic 2015
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PLoS Biol. 2006
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J. Cell Biol. 1988
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Mol. Biol. Cell 2007
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Keen, JH

J. Cell Biol. 1987
17267500 Downregulation of CD4 by human immunodeficiency virus type 1 Nef is dependent on clathrin and involves direct interaction of Nef with the AP2 clathrin adaptor

Chaudhuri, R, Lindwasser, OW, Smith, WJ, Hurley, JH, Bonifacino, JS

J. Virol. 2007
16516836 Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly

Edeling, MA, Mishra, SK, Keyel, PA, Steinhauser, AL, Collins, BM, Roth, R, Heuser, JE, Owen, DJ, Traub, LM

Dev. Cell 2006
9812899 A structural explanation for the recognition of tyrosine-based endocytotic signals

Owen, DJ, Evans, PR

Science 1998
11071885 Multiple C-terminal motifs of the 46-kDa mannose 6-phosphate receptor tail contribute to efficient binding of medium chains of AP-2 and AP-3

Storch, S, Braulke, T

J. Biol. Chem. 2001
24186068 Cargo recognition in clathrin-mediated endocytosis

Traub, LM, Bonifacino, JS

Cold Spring Harb Perspect Biol 2013
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Owen, DJ, Collins, BM, Evans, PR

Annu. Rev. Cell Dev. Biol. 2004
20351096 Alpha-AP-2 directs myosin VI-dependent endocytosis of cystic fibrosis transmembrane conductance regulator chloride channels in the intestine

Collaco, A, Jakab, R, Hegan, P, Mooseker, M, Ameen, N

J. Biol. Chem. 2010
2257624 Transferrin receptor internalization sequence YXRF implicates a tight turn as the structural recognition motif for endocytosis

Collawn, JF, Stangel, M, Kuhn, LA, Esekogwu, V, Jing, SQ, Trowbridge, IS, Tainer, JA

Cell 1990
17713526 Integrating molecular and network biology to decode endocytosis

Schmid, EM, McMahon, HT

Nature 2007
1535555 A novel di-leucine motif and a tyrosine-based motif independently mediate lysosomal targeting and endocytosis of CD3 chains

Letourneur, F, Klausner, RD

Cell 1992
7569928 Interaction of tyrosine-based sorting signals with clathrin-associated proteins

Ohno, H, Stewart, J, Fournier, MC, Bosshart, H, Rhee, I, Miyatake, S, Saito, T, Gallusser, A, Kirchhausen, T, Bonifacino, JS

Science 1995
12086608 Molecular architecture and functional model of the endocytic AP2 complex

Collins, BM, McCoy, AJ, Kent, HM, Evans, PR, Owen, DJ

Cell 2002
19140243 A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex

Kelly, BT, McCoy, AJ, Späte, K, Miller, SE, Evans, PR, Höning, S, Owen, DJ

Nature 2008
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