Molecular switches involving the AP-2 β2 appendage regulate endocytic cargo selection and clathrin coat assembly

Melissa A Edeling, Sanjay K Mishra, Peter Keyel, Amie L Steinhauser, B M Collins, Robyn Roth, John E Heuser, David J Owen, Linton M Traub

Research output: Contribution to journalArticle

Abstract

Clathrin-associated sorting proteins (CLASPs) expand the repertoire of endocytic cargo sorted into clathrin-coated vesicles beyond the transmembrane proteins that bind physically to the AP-2 adaptor. LDL and GPCRs are internalized by ARH and β-arrestin, respectively. We show that these two CLASPs bind selectively to the AP-2 β2 appendage platform via an α-helical [DE] nX 1-2 FXX[FL]XXXR motif, and that this motif also occurs and is functional in the epsins. In β-arrestin, this motif maintains the endocytosis-incompetent state by binding back on the folded core of the protein in a β strand conformation. Triggered via a β-arrestin/ GPCR interaction, the motif must be displaced and must undergo a strand to helix transition to enable the β2 appendage binding that drives GPCR-β-arrestin complexes into clathrin coats. Another interaction surface on the β2 appendage sandwich is identified for proteins such as eps15 and clathrin, suggesting a mechanism by which clathrin displaces eps15 to lat
Original languageEnglish
Pages (from-to)329-342
JournalDevelopmental Cell
StatePublished - 2006

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    Edeling, M. A., Mishra, S. K., Keyel, P., Steinhauser, A. L., Collins, B. M., Roth, R., Heuser, J. E., Owen, D. J., & Traub, L. M. (2006). Molecular switches involving the AP-2 β2 appendage regulate endocytic cargo selection and clathrin coat assembly. Developmental Cell, 329-342.