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Arrestins

Structure and Function in Vision and Beyond

1st Edition - March 20, 2022

Editor: Vsevolod V. Gurevich

Paperback ISBN:

9 7 8 - 0 - 3 2 3 - 8 5 7 5 6 - 7

eBook ISBN:

9 7 8 - 0 - 3 2 3 - 8 5 6 3 5 - 5

Arrestins: Structure and Function in Vision and Beyond examines the structural basis of the function of arrestin proteins in the brain. Linking basic, translational and clinical… Read more

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Arrestins: Structure and Function in Vision and Beyond examines the structural basis of the function of arrestin proteins in the brain. Linking basic, translational and clinical research, this volume begins with history and basic signaling principles and then expands to the use of proteins as potential therapeutic targets. Multiple cellular activities are detailed, including activation, signaling, GPCR endocytosis, and ERK signaling, with chapters examining both visual and non-visual arrestins. Experts in their respective fields are featured throughout, making this book essential reading for anyone who wants to explore the basic science underlying these signaling proteins.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Chapter 1. History of arrestins
Chapter 2. Arrestin-mediated trafficking and compartmentalized biology of GPCRs
1. Introduction
2. Arrestin as a scaffold for endocytic proteins
3. Molecular determinates guiding receptor trafficking: Class A versus Class B GPCRs
4. Arrestin as a spatiotemporal regulator of G protein signaling
5. Arrestin-dependent ubiquitination and postendocytic sorting
6. Conclusion
Chapter 3. The structural basis of arrestin–GPCR interactions
1. GPCRs go through an activation–inactivation cycle
2. Inactive arrestins adopt an autoinhibitory conformation
3. Binding of a phosphorylated GPCR C-tail peptide is sufficient to activate arrestin
4. The active state arrestin crest loops bind the cytoplasmic surface of active state GPCRs
5. Advancements in cryo-EM have enabled the recent determination of additional GPCR-G protein and GPCR–arrestin structures
6. Finger loop variability and dynamics contribute to β-arrestin's GPCR-binding promiscuity
7. Signaling selectivity: phosphorylation bar codes and structural determinants of biased signaling
Chapter 4. Arrestin scaffolding and activation of MAPK cascades
1. Introduction
2. Arrestin and the Raf-MEK-ERK cascade
3. Arrestin and the ASK1-MKK4/7-JNK3 cascade
4. Arrestin and the ASK1-MKK3/6-p38 cascade
5. Concluding Remarks
Chapter 5. β-Arrestins as regulators of key metabolic processes
1. Introduction
2. Canonical functions of βarr2 in disrupting signaling through metabolically important GPCRs
3. Noncanonical functions of β-arrestins: modulation of the activity of cytoplasmic signaling proteins
4. Noncanonical functions of β-arrestins: role of nuclear βarr1 in regulating metabolic processes
5. Concluding remarks
Chapter 6. Arrestins in cardiac function: the current state of affairs
1. Introduction
2. Cardiac adrenergic receptors and βarrestins
3. Cardiac angiotensin II receptors and βarrestins
4. Other cardiac GPCRs and βarrestins
5. Conclusions and future perspectives
Chapter 7. Signaling-biased arrestin-based molecular tools
1. Introduction
2. Structure of arrestins: functional role of select elements
3. Altered receptor specificity of arrestins can bias signaling
4. Manipulation of GPCR trafficking by arrestin mutants can also bias signaling
5. Biasing signaling by altering effector binding
6. Limitations for construction of designer arrestins: cross-talk in the arrestin molecule
7. Barcode hypothesis and its implications for biased signaling
8. What needs to be done next to create signaling-biased arrestin-based tools?
Index