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Homo sapiens
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Beta arrestins 1 and 2 are required for the endocytosis and downregulation of numerous GPCRs including ADRB2, CHRM2, FZD, C5aR and many others (Ferguson et al, 1995; Goodman et al, 1995; Chen et al, 2003; Gurevich et al, 1995; Braun et al, 2003; reviewed in Kovacs et al, 2009; Traub and Bonifacino, 2013). Beta-arrestin mediated downregulation of GPCRs is modulated by receptor phosphorylation status (see for instance Fessart et al, 2007; Braun et al, 2003; reviewed in Gurevich and Gurevich, 2006). In addition to recognizing GPCR cargo, beta-arrestins also bind directly to the AP-2 complex, thus mediating the recruitment of cargo into nascent clathrin coated vesicles (Edeling et al, 2006; Schmid et al, 2006; reviewed in Traub and Bonifacino, 2013; Kang et al, 2014). A recent study has shown that in addition to mediating GPCR endocytosis, beta-arrestin2 can be recruited to CCPs after dissociation from ADRB2 to promote MAPK signaling, highlighting a role for CCPs as signaling microdomains (Eichel et al, 2016).

Literature References
PubMed ID Title Journal Year
12958364 Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4

Chen, W, ten Berge, D, Brown, J, Ahn, S, Hu, LA, Miller, WE, Caron, MG, Barak, LS, Nusse, R, Lefkowitz, RJ

Science 2003
8553074 Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization

Ferguson, SS, Downey, WE, Colapietro, AM, Barak, LS, Ménard, L, Caron, MG

Science 1996
24680432 Role of ?-arrestins and arrestin domain-containing proteins in G protein-coupled receptor trafficking

Kang, DS, Tian, X, Benovic, JL

Curr. Opin. Cell Biol. 2014
16460808 The structural basis of arrestin-mediated regulation of G-protein-coupled receptors

Gurevich, VV, Gurevich, EV

Pharmacol. Ther. 2006
8837779 Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor

Goodman, OB, Krupnick, JG, Santini, F, Gurevich, VV, Penn, RB, Gagnon, AW, Keen, JH, Benovic, JL

Nature 1996
16903783 Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly

Schmid, EM, Ford, MG, Burtey, A, Praefcke, GJ, Peak-Chew, SY, Mills, IG, Benmerah, A, McMahon, HT

PLoS Biol. 2006
26829388 ?-Arrestin drives MAP kinase signalling from clathrin-coated structures after GPCR dissociation

Eichel, K, Jullié, D, von Zastrow, M

Nat. Cell Biol. 2016
12464600 Phosphorylation of key serine residues is required for internalization of the complement 5a (C5a) anaphylatoxin receptor via a beta-arrestin, dynamin, and clathrin-dependent pathway

Braun, L, Christophe, T, Boulay, F

J. Biol. Chem. 2003
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
7822302 Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors

Gurevich, VV, Dion, SB, Onorato, JJ, Ptasienski, J, Kim, CM, Sterne-Marr, R, Hosey, MM, Benovic, JL

J. Biol. Chem. 1995
24186068 Cargo recognition in clathrin-mediated endocytosis

Traub, LM, Bonifacino, JS

Cold Spring Harb Perspect Biol 2013
17456551 Src-dependent phosphorylation of beta2-adaptin dissociates the beta-arrestin-AP-2 complex

Fessart, D, Simaan, M, Zimmerman, B, Comeau, J, Hamdan, FF, Wiseman, PW, Bouvier, M, Laporte, SA

J. Cell. Sci. 2007
19853559 Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways

Kovacs, JJ, Hara, MR, Davenport, CL, Kim, J, Lefkowitz, RJ

Dev. Cell 2009
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