Biology Reference
In-Depth Information
CHAPTER SIX
-Arrestins: Modulators of Small
GTPase Activation and Function
b
Audrey Claing
Department of Pharmacology, Universit´ de Montr´al, Montr´al, Quebec, Canada
Contents
1.
Introduction
150
1.1 The family of GTPases
150
1.2 Modes of regulation of GTPase activity
152
2. Ras Family GTPases
154
2.1 Ras and the MAPK pathway
154
2.2 Ral A multifunctional GTPase
155
3. Rho Family GTPases
157
3.1 Rho and b-arrestin modulation of stress fiber formation
158
3.2 Rac The GTPase associated with membrane ruffling and protrusions
160
3.3 Cdc42 and filopodia formation
161
4. Rab Family GTPases
162
4.1 Colocalization of Rabs with receptors and b-arrestin
163
4.2 Modulation of Rab function through interaction
164
5. ARF Family GTPases
164
5.1 ARF6 and receptor endocytosis
165
5.2 Remodeling of the actin cytoskeleton via b-arrestin and ARF6
166
6. Ran Family GTPases
166
7. Perspectives and Future Directions
167
7.1 Defining the role of b-arrestin 1 and b-arrestin 2
167
7.2 Identification of the mechanisms whereby b-arrestins regulate
GTPase function
168
8. Conclusions
169
References
169
Abstract
Most cellular events responsible for accurate G protein-coupled receptor trafficking
involve small GTP-binding proteins. For example, trafficking of receptors via the
endocytic and exocytic pathways requires activation of ADP-ribosylation factors and
Rab proteins, while receptor-mediated complex responses such as migration are well
characterized to be dependent upon Rho family members. Because b-arrestin proteins
are recruited to activated receptors and now considered as key signaling molecules,
 
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