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Publication Abstract from PubMed

Coat complexes sort protein cargoes into vesicular transport pathways. An emerging class of coat components has been the GAPs (GTPase activating proteins) that act on the ARF (ADP-Ribosylation factor) family of small GTPases. ACAP1 (ArfGAP with Coil coil, Ankyrin repeat, and PH domain protein 1) is an ARF6 GAP that also acts as a key component of a recently defined clathrin complex for endocytic recycling. Phosphorylation by Akt has been shown to enhance cargo binding by ACAP1 in explaining how integrin recycling is an example of regulated transport. We now shed further mechanistic insights into how this regulation is achieved at the level of cargo binding by ACAP1. We initially define a critical sequence in the cytoplasmic domain of integrin beta1 recognized by ACAP1, and show that this sequence acts as a recycling sorting signal. We then pursue a combination of structural, modeling and functional studies, which suggest that phosphorylation of ACAP1 relieves a localized mechanism of auto-inhibition in regulating cargo binding. Thus, we have elucidated a key regulatory juncture that controls integrin recycling, and also advanced the understanding of how regulated cargo binding can lead to regulated transport.

Mechanistic insights into regulated cargo binding by ACAP1.,Bai M, Pang X, Lou J, Zhou Q, Zhang K, Ma J, Li J, Sun F, Hsu V J Biol Chem. 2012 May 29. PMID:22645133^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.