Biology Reference
In-Depth Information
CHAPTER ONE
Arrestins Come of Age: A Personal
Historical Perspective
Robert J. Lefkowitz
*
,†
*
Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC, USA
†
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, USA
Contents
1.
Introduction
4
2.
Prehistory
of Arrestins
4
“
”
3.
A Family of 7 Transmembrane Receptors
5
4.
The GRK and Arrestin Families
5
5.
Arrestins and Desensitization
8
6.
Arrestins and Endocytosis
8
7.
Arrestins and Signaling
9
8.
Biased Signaling
10
9.
Bar Code Hypothesis
12
10.
Other Receptors, Other Functions
13
11.
Future Perspectives
14
References
14
Abstract
Visual arrestin and the two b-arrestins (1 and 2) were originally discovered 25
-
30 years
ago in the context of their ability to desensitize phosphorylated G protein-coupled
receptors (rhodopsin and the b2-adrenergic receptor, respectively). A fourth retinal-
specific member of the family (X-arrestin) was discovered later. Over the past
10
-
15 years, however, it has become clear that these versatile molecules subserve a host
of other roles in modulating and mediating the function of most GPCRs as well as other
types of receptors. Functioning as multifunctional adaptor proteins, the b-arrestins also
play prominent roles in receptor endocytosis, signaling, trafficking, and ubiquitination
among others. Here, I provide a brief personal perspective on how the field has evolved
since its inception and speculate on future directions.
