The Molecular Biology of Arrestins

Contributors

Preface

Part I: Perspective - The Duality of Arrestin Function

Chapter One. Arrestins Come of Age: A Personal Historical Perspective

1 Introduction

2 “Prehistory” of Arrestins

3 A Family of 7 Transmembrane Receptors

4 The GRK and Arrestin Families

5 Arrestins and Desensitization

6 Arrestins and Endocytosis

7 Arrestins and Signaling

8 Biased Signaling

9 Bar Code Hypothesis

10 Other Receptors, Other Functions

11 Future Perspectives

References

Part II: The Molecular Biology of Arrestins

Chapter Two. True Arrestins and Arrestin-Fold Proteins: A Structure-Based Appraisal

Abbreviations

1 Introduction

2 True Arrestins: A Structure Adapted to Multiple Scaffolding

3 Novel Arrestin-Related Proteins

4 Other Arrestin-Fold Proteins

5 Are Arrestins and Arrestin-Fold Proteins Related by a Shared Mechanism for Their Function?

6 Conclusion and Perspectives

References

Chapter Three. Structural Determinants of Arrestin Functions

1 Introduction

2 What the Crystal Structure Reveals, and What It Does Not

3 How Do Arrestins Fit Receptors?

4 Interactions with Other Signaling Proteins

5 Designing Signaling-Biased Arrestin Mutants

6 Conclusions: Where Do We Go from Here?

Acknowledgments

References

Chapter Four. Arrestins: Role in the Desensitization, Sequestration, and Vesicular Trafficking of G Protein-Coupled Receptors

1 Introduction

2 Arrestins in GPCR Desensitization

3 Arrestins in GPCR Trafficking

4 Conclusions

Acknowledgments

References

Chapter Five. Arrestins as Regulators of Kinases and Phosphatases

1 Introduction

2 Arrestins as GPCR Effectors

3 Positive and Negative Regulation of Kinase Pathways

4 Arrestin-Regulated Kinase and Phosphatase Pathways

5 Conclusions

Acknowledgments

References

Chapter Six. β-Arrestins: Modulators of Small GTPase Activation and Function

1 Introduction

2 Ras Family GTPases

3 Rho Family GTPases

4 Rab Family GTPases

5 ARF Family GTPases

6 Ran Family GTPases

7 Perspectives and Future Directions

8 Conclusions

References

Chapter Seven. Arrestins and Protein Ubiquitination

1 Introduction

2 Ubiquitination of Arrestins

3 Deubiquitination of Arrestins

4 Arrestins Act as Adaptors for Ubiquitination

5 Arrestins and Seven-Transmembrane Receptor Deubiquitination

6 Arrestin-Like Proteins

7 Conclusions

Acknowledgment

References

Chapter Eight. Arrestins in Actin Reorganization and Cell Migration

1 Introduction

2 β-Arrestins as Regulators of Gradient Sensing for Chemokine Receptors

3 β-Arrestins as Regulators of Actin Assembly

4 Regulation of Kinase Activities by β-Arrestins

5 Additional Roles for β-Arrestins and Chemotaxis In Vivo

6 Role of β-Arrestin-Dependent Chemotaxis in Health and Disease

7 Concluding Remarks

References

Part III: The Physiological Roles of Arrestins

Chapter Nine. The Role of Arrestins in Development

1 Introduction

2 β-Arrestins in Model Organisms

3 The Function of Arrestins in Invertebrates

4 β-Arrestins in Vertebrate Development

5 Conclusions

Acknowledgments

References

Chapter Ten. The Role of Arrestins in Visual and Disease Processes of the Eye

1 Visual Arrestin Nomenclature

2 The Function of Visual Arrestins in Quenching Phototransduction

3 Splice Variants of Arrestin1

4 Arrestins in Cone Photoreceptors

5 Translocation of Visual Arrestins

6 New Roles for Arrestin1 in the Retina

7 Arrestins in Disease Processes in the Eye

8 The Future for Visual Arrestins

References

Chapter Eleven. β-Arrestins in the Central Nervous System

1 Introduction: Arrestins and GRK in the Central Nervous System

2 Arrestins and GRK in Dopaminergic Neurotransmission

3 Arrestins in Serotonergic Neurotransmission

4 Arrestins in Noradrenergic Neurotransmission

5 Arrestins in Opioid Receptor Signaling

6 Arrestins and Corticotropin Receptors

7 Other β-arrestin-Dependent Behavior

8 Conclusions

Acknowledgment

References

Chapter Twelve. Arrestins in the Cardiovascular System

1 Introduction

2 Cardiovascular Adrenergic Receptors and βarrs

3 Cardiovascular Angiotensin II Receptors and βarrs

4 Other Cardiovascular GPCRs and βarrs

5 Cardiovascular Non-GPCRs and βarrs

6 Biased Agonism/Antagonism of Cardiovascular GPCR Ligands

7 Perspectives and Future Directions

8 Conclusions

References

Chapter Thirteen. Arrestins in Bone

Abbreviations

1 Introduction

2 Arrestin Signaling: A New Dimension to GCPR Signaling in Bone

3 Functional Selectivity in Bone

4 Arrestin Signaling Effects in Bone

5 Perspectives and Future Directions

6 Conclusions

Acknowledgments

References

Chapter Fourteen. β-Arrestins in the Immune System

1 Introduction

2 β-Arrestins in Innate Immunity

3 β-Arrestins in Adaptive Immunity

4 β-Arrestins and Structural Cells

5 β-Arrestins Regulate Immune Signaling Pathways

6 Role of β-Arrestins in Human Diseases

7 β-Arrestins in Therapeutic Development for Inflammatory Diseases

References

Chapter Fifteen. The Role of β-Arrestins in Cancer

1 Introduction

2 ARRBs and Cancer-Associated Cell Phenotypes

3 The Role of ARRBs in Cancer

4 Conclusions

Acknowledgments

References

Chapter Sixteen. Arrestins in Metabolic Regulation

1 A Short Introduction to Metabolic Regulation

2 Functional Roles of β-Arrestins in Regulation of Whole-Body Energy Balance and Body Weight Control

3 Functional Role of β-Arrestins in Regulation of Carbohydrate and Lipid Homeostasis

4 Conclusions

References

Part IV: The Future - The Potential for Arrestin-based Therapeutics

Chapter Seventeen. Systems Analysis of Arrestin Pathway Functions

1 G Protein-Coupled Receptor Signaling Activity

2 Signaling Diversity Among GPCRs

3 Systems Analysis of Receptor Signaling Systems

4 Functional Analyses of Arrestin Signaling Paradigms

5 Conclusions

Acknowledgments

References

Chapter Eighteen. Arrestin Pathways as Drug Targets

1 Introduction

2 Biased GPCR Agonism

3 The Many Faces of Arrestin-Dependent Biased Agonism

4 The Conserved Arrestin-Dependent Signaling Repertoire

5 Conclusions

Acknowledgments

References

Index