Molecular Switches Involving the AP-2 Beta 2 Appendage Regulate Endocytic Cargo Selection and Clathrin Coat Assembly

Edeling, Melissa A., Mishra, Sanjay K., Keyel, Peter A., Steinhauser, Amie L., Collins, Brett M., Roth, Robyn, Heuser, John E., Owen, David J. and Traub, Linton M. (2006) Molecular Switches Involving the AP-2 Beta 2 Appendage Regulate Endocytic Cargo Selection and Clathrin Coat Assembly. Developmental Cell, 10 3: 329-342. doi:10.1016/j.devcel.2006.01.016


Author Edeling, Melissa A.
Mishra, Sanjay K.
Keyel, Peter A.
Steinhauser, Amie L.
Collins, Brett M.
Roth, Robyn
Heuser, John E.
Owen, David J.
Traub, Linton M.
Title Molecular Switches Involving the AP-2 Beta 2 Appendage Regulate Endocytic Cargo Selection and Clathrin Coat Assembly
Journal name Developmental Cell   Check publisher's open access policy
ISSN 1534-5807
Publication date 2006-03-01
Year available 2006
Sub-type Article (original research)
DOI 10.1016/j.devcel.2006.01.016
Open Access Status Not yet assessed
Volume 10
Issue 3
Start page 329
End page 342
Total pages 14
Place of publication Cambridge
Publisher Elsevier
Language eng
Subject 0601 Biochemistry and Cell Biology
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 beta-arrestin, respectively. We show that these two CLASPs bind selectively to the AP-2 beta 2 appendage platform via an alpha-helical [DE](n)X1-2FXX[FL]XXXR motif, and that this motif also occurs and is functional in the epsins. In beta-arrestin, this motif maintains the endocytosis-incompetent state by binding back on the folded core of the protein in a beta strand conformation. Triggered via a beta-arrestin/GPCR interaction, the motif must be displaced and must undergo a strand to helix transition to enable the beta 2 appendage binding that drives GPCR-beta-arrestin complexes into clathrin coats. Another interaction surface on the beta 2 appendage sandwich is identified for proteins such as eps15 and clathrin, suggesting a mechanism by which clathrin displaces eps15 to lattice edges during assembly.
Keyword Cell Biology
Developmental Biology
Protein-coupled Receptors
Accessory Protein
Mediated Endocytosis
Crystal-structure
Alpha-appendage
Adapter-protein
Structural Explanation
Functional Dissection
Vesicle Endocytosis
Arrestin
Q-Index Code C1
Grant ID R01DK53249
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 20 Sep 2007, 04:00:49 EST