Arrestins: Role in the Desensitization, Sequestration, and Vesicular Trafficking of G Protein-Coupled Receptors - Progress in Molecular Biology and Translational Science - page 89

CHAPTER FOUR

Arrestins: Role in the
Desensitization, Sequestration,
and Vesicular Trafficking of
G Protein-Coupled Receptors

Cornelia Walther *

, †
* J. Allyn Taylor Centre for Cell Biology, Robarts Research Institute, Western University Canada, London,
Ontario, Canada
† Department of Physiology and Pharmacology, Western University Canada, London, Ontario, Canada

, † , Stephen S.G. Ferguson *

Contents
1. Introduction 93

2. Arrestins in GPCR Desensitization 95

3. Arrestins in GPCR Trafficking 99

3.1 Sequestration 100

3.2 Postendocytic vesicular trafficking of GPCRs 104

4. Conclusions 107

Acknowledgments 107

References 107

Abstract
Over the years, b-arrestins have emerged as multifunctional molecular scaffolding pro-
teins regulating almost every imaginable G protein-coupled receptor (GPCR) function.
Originally discovered as GPCR-desensitizing molecules, they have been shown to also
serve as important regulators of GPCR signaling, sequestration, and vesicular trafficking.
This broad functional role implicates b-arrestins as key regulatory proteins for cellular
function. Hence, this chapter summarizes the current understanding of the b-arrestin
family s unique ability to control the kinetics as well as the extent of GPCR activity at

the level of desensitization, sequestration, and subsequent intracellular trafficking.

'

1. INTRODUCTION

G protein-coupled receptors (GPCRs) are integral membrane pro-
teins that represent the largest and functionally most diverse family of
cell-surface receptor proteins. Members of this family share a common