Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity

Audrey Claing, Stephen J. Perry, Mircea Achiriloaie, Julia K L Walker, Joseph P. Albanesi, Robert J. Lefkowitz, Richard T. Premont

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

Recently, we identified a GTPase-activating protein for the ADP ribosylation factor family of small GTP-binding proteins that we call GIT1. This protein initially was identified as an interacting partner for the G protein-coupled receptor kinases, and its overexpression was found to affect signaling and internalization of the prototypical β2-adrenergic receptor. Here, we report that GIT1 overexpression regulates internalization of numerous, but not all, G protein-coupled receptors. The specificity of the GIT1 effect is not related to the type of G protein to which a receptor couples, but rather to the endocytic route it uses. GIT1 only affects the function of G protein-coupled receptors that are internalized through the clathrin-coated pit pathway in a β-arrestin- and dynamin-sensitive manner. Furthermore, the GIT1 effect is not limited to G protein-coupled receptors because overexpression of this protein also affects internalization of the epidermal growth factor receptor. However, constitutive agonist-independent internalization is not regulated by GIT1, because transferrin uptake is not affected by GIT1 overexpression. Thus, GIT1 is a protein involved in regulating the function of signaling receptors internalized through the clathrin pathway and can be used as a diagnostic tool for defining the endocytic pathway of a receptor.

Original languageEnglish (US)
Pages (from-to)1119-1124
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number3
DOIs
StatePublished - Feb 1 2000

ASJC Scopus subject areas

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