Biology Reference
In-Depth Information
CHAPTER EIGHT
Arrestins in Actin Reorganization
and Cell Migration
Kathryn A. DeFea
Biomedical Sciences Division, School of Medicine, University of California Riverside, Riverside,
California, USA
Contents
1.
Introduction
206
2.
-Arrestins as Regulators of Gradient Sensing for Chemokine Receptors
206
b
2.1 Receptor turnover
208
2.2 Differential signaling in response to ligand multimers
208
3.
b -Arrestins as Regulators of Actin Assembly
209
3.1 The cofilin pathway: Creating new actin seeds
210
3.2 Filamin and other actin-binding proteins
212
3.3 RhoA GTPases
212
4. Regulation of Kinase Activities by b -Arrestins
214
4.1
b -Arrestin-dependent ERK1/2 activity
215
4.2
-Arrestin/Src complexes and chemotaxis
216
b
5. Additional Roles for b -Arrestins and Chemotaxis In Vivo
217
6. Role of
-Arrestin-Dependent Chemotaxis in Health and Disease
218
b
7. Concluding Remarks
219
References
220
Abstract
Arrestins have emerged as important regulators of actin reorganization and cell migra-
tion. Both in their classical roles as mediators of receptor desensitization and internal-
ization, and in their newer role as signaling scaffolds, b -arrestins help orchestrate the
cellular response to chemotactic signals. However, there is still a considerable amount
to be learned about the precise molecular mechanisms underlying these processes. This
review discusses how, by regulating receptor internalization and by scaffolding of sig-
naling molecules in discrete cellular locations, arrestins facilitate gradient sensing and
cytoskeletal reorganization, ultimately resulting in cell migration. In addition, putative
new targets of b -arrestin regulation that may play important roles in cell migration
are discussed, as continued research on these targets may provide important details
to fill in the current gaps in our understanding of these processes.
 
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