The Role of Arrestins in Development - Progress in Molecular Biology and Translational Science - page 217

CHAPTER NINE

The Role of Arrestins
in Development

Melanie Philipp * , Tama Evron † , Marc G. Caron † , ‡ ,}
* Institute of Biochemistry and Molecular Biology, Ulm University, Ulm, Germany
† Department of Cell Biology, Duke University Medical Center, Durham North Carolina, USA
‡ Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
} Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, USA

Contents
1.

Introduction 226

2. b -Arrestins in Model Organisms 228

3. The Function of Arrestins in Invertebrates 229

4. b-Arrestins in Vertebrate Development 230

4.1 barr1 in hematopoiesis 230

4.2 barr2 in Wnt signaling 231

4.3 barrs in Hh signaling 234

5. Conclusions 238

Acknowledgments 238

References 238

Abstract
b

-Arrestins are versatile scaffolding proteins that are involved in orchestrating a large
number of signaling cascades. Because b-arrestin 1 and b-arrestin 2 are individually dis-
pensable during development, it has long been assumed that b-arrestins do not play an
important role during embryogenesis. Nonetheless, there is growing evidence from
both invertebrate and vertebrate animal models that b-arrestins are integral regulators
of developmental pathways. They are involved in diverse processes such as early hema-
topoiesis, establishment of axial development axes, cell convergence and extension
movements leading to axial elongation, musculoskeletal and craniofacial development,
cell proliferation, and neuronal development. Most of the developmental roles of
arrestins involve interactions with or regulation of novel non-G protein-coupled recep-
tor partners, such as atypical seven-transmembrane receptors, small G proteins,
and nuclear transcription factors, revealing surprising diversity in arrestin function.
In contrast to their largely overlapping roles in G protein-coupled receptor desensitiza-
tion and internalization, study of the role of arrestins in development has demonstrated
marked functional specialization of the b-arrestin 1 and 2 isoforms.