Zinc Signaling

Foreword

Contents

Chapter 1: Opening the Second Era of Zinc Signaling Study

1.1 Introduction

1.2 Progresses, Questions, and Directions

References

Chapter 2: Regulation of Cellular Zinc Ions and Their Signaling Functions

2.1 Proteins Regulating Zinc: Buffering and Muffling in Cellular Zinc Homeostasis

2.2 Metallothioneins

2.3 Zinc Transporters

2.3.1 ZnTs (Solute Carrier Family SLC30A1-10)

2.3.2 ZIPs (Zrt/Irt-Like Proteins) (Solute Carrier Family SLC39A1-14)

2.4 MTF-1

2.5 Signaling with Inorganic Ions: Ca2+ and Zn2+

2.6 Zinc Regulating Proteins (Zinc/Zn2+ Signaling)

2.6.1 Intracellular Regulation

2.6.2 Extracellular Regulation

2.7 Zinc Functions in Health and Disease

References

Chapter 3: Zinc Transporter Proteins: A Review and a New View from Biochemistry

3.1 Introduction

3.2 History of ZNT and ZIP Family Proteins

3.3 ZNT Transporters

3.3.1 Biochemical and Structural Properties of Bacterial ZNT Homologs

3.3.2 Properties of ZNT Transporter Proteins

3.3.3 Biochemical Characterization of the ZNT Subgroups

3.3.3.1 ZNT1 and ZNT10 Subgroup

3.3.3.2 ZNT2, ZNT3, ZNT4, and ZNT8 Subgroup

3.3.3.3 ZNT5 and ZNT7 Subgroup

3.3.3.4 ZNT6 Subgroup

3.4 ZIP Transporters

3.4.1 Biochemical and Structural Properties of Bacterial ZIP Homologs

3.4.2 Properties of ZIP Family Proteins

3.4.3 Biochemical Characterization of the ZIP Subfamilies

3.4.3.1 ZIP-I Subfamily

3.4.3.2 ZIP–II Subfamily

3.4.3.3 gufA Subfamily

3.4.4 Biochemical Characterization of LIV-1 Subfamily

3.4.4.1 ZIP4 and ZIP12 Subgroup

3.4.4.2 ZIP8 and ZIP14 Subgroup

3.4.4.3 ZIP5, ZIP6, and ZIP10 Subgroup

3.4.4.4 ZIP7 and ZIP13 Subgroup

3.5 Concluding Remarks and Perspectives

References

Chapter 4: The Metallothionein-Zinc Landscape: How It Shapes Antimicrobial Immunity

4.1 Introduction

4.2 Low Zinc Spells a High Infection Risk

4.3 The Zinc Pill: To Take or Not to Take?

4.4 Zinc: A Prominent Driver on the Road to Innate Defense

4.5 The MT-Zinc Immune-Landscape: An Old Axis with a New Tale

4.6 The MT-Zinc Axis in Infection

4.6.1 Bacterial Infection

4.6.2 Fungal Infection

4.6.3 Viral and Parasitic Infections

4.7 Survival Edge: Microbes (Aim to) Get the Upper Hand

4.8 Concluding Remarks

References

Chapter 5: Role of Zinc Signaling in Mast Cell, Basophil, T Cell, and B Cell

5.1 Introduction

5.2 Zinc Homeostasis

5.3 Role of Zinc as a Second Messenger

5.4 Zinc Signaling Mediated by Antigen Receptors

5.4.1 Fc?RI-Mediated Zinc Signaling

5.4.2 BCR-Mediated Zinc Signaling

5.4.3 TCR-Mediated Zinc Signaling

5.5 Role of Zinc and Zinc Signaling in Cytokine Production

5.5.1 Role of Zinc in Mast Cell-Mediated Cytokine Production

5.5.2 Role of Zinc in Basophil-Mediated Cytokine Production

5.6 Zinc Wave Is a Key Regulator of Cytokine Production in Immune Cells

5.7 Perspective

References

Chapter 6: Review: The Role of Zinc Signaling in Reproduction

6.1 Zinc Signaling in Female Reproduction

6.1.1 Gamete Genesis

6.1.2 Oocyte Activation and Fertilization

6.1.3 The Role of Zinc Signaling in Fertilization: The Discovery of the “Zinc Sparks”

6.1.4 The Expression and Function of Zinc Transporters in Mammalian Oocytes

6.1.5 Pregnancy: Embryo Implantation, Decidualization, and Placentation

6.1.6 Zinc and Pregnancy

6.2 Zinc Signaling in Male Reproduction

References

Chapter 7: Zinc Signaling in Skeletal Muscle

7.1 Introduction

7.2 Muscle Contraction

7.3 Muscle Growth

7.4 Skeletal Muscle Repair from Injury, Atrophy, and Cachexia

7.5 Skeletal Muscle-Based Glucose Metabolism

7.6 Future Perspectives

References

Chapter 8: Zinc Signaling in Aging Heart Function

8.1 Introduction

8.2 Role of Zinc in Mammalian Heart Function

8.3 Aging and Insufficient Heart Function

8.4 Role of the Mitochondria in Aging Heart

8.5 Role of Zinc in Mitochondrial Dysfunction in Aging Heart

8.6 Role of Zinc Transporters in Mammalian Heart Function

8.7 Role of Zinc Transporter ZIP14 in Aging Mammalian Heart Function

8.8 Conclusion

References

Chapter 9: Zinc Signaling in the Life and Death of Neurons

9.1 Zinc Rocks!

9.2 Zinc Is a Neurotransmitter

9.3 Intracellular Zinc Signaling

9.3.1 Translocation of Synaptic Zinc

9.3.2 Intracellular Liberation of Zinc

9.3.3 A Zinc/Potassium Continuum in Neuronal Cell Death

9.4 Tapping the Zinc/Potassium Continuum as a Neuroprotective Strategy

9.5 Concluding Remarks

References

Chapter 10: Possible Therapeutic Roles of Metallothionein-3 and Zinc in Endosome-Autophagosome-Lysosome Pathway (EALP) Dysfunction in Astrocytes

10.1 Introduction

10.2 Contributors to Lysosomal Dysfunction in Aging-Related Neurodegenerative Diseases and Their Mechanisms

10.3 Possible Measures to Restore Lysosomal Function

10.4 Emerging Role of Metallothionein-3 (MT3) in Regulation of Endocytosis and Lysosome Functions in Astrocytes

10.5 Measures Increasing Cytosolic and/or Lysosomal Free Zinc Levels May Help Overcome Lysosomal Dysfunction

10.6 Conclusions

References

Chapter 11: Zinc in Neurodegeneration

11.1 Introduction

11.2 How Does Zinc Contribute to Neurodegeneration?

11.2.1 Zinc and Autophagy

11.2.2 Zinc and Protein Aggregation

11.2.3 Zinc and Oxidative Stress

11.2.4 Zinc and Synaptic Function/ Learning and Memory

11.2.5 Zinc, Excitotoxicity and Mitochondria

11.2.6 Zinc and Inflammation

11.2.7 Zinc and Alzheimer’s Disease

11.2.8 Zinc and Parkinson’s Disease

11.2.9 Zinc and Amyotrophic Lateral Sclerosis

11.2.10 Zinc and Ageing

11.2.11 Zinc and Traumatic Brain Injury

11.3 Conclusion

References

Chapter 12: Role of Zinc Transporters in Type 2 Diabetes and Obesity

12.1 Zinc and Pancreatic ? Cells

12.2 Zinc Deficiency and Diabetes

12.3 Physiological Functions of Zinc Transporters

12.4 Structure and Function of ZnT8

12.5 The Role of ZnT8 in Glucose Homeostasis

12.6 Reconsideration of SLC30A8 Activity and the Risk of Diabetes

12.7 Zinc Transporter ZIP13 Inhibits Adipocyte Browning

12.8 Therapeutic Application of Zinc Transporters Toward Obesity and Diabetes

References

Chapter 13: Zinc Signals in Immunology

13.1 Zinc Signals in Immunology

13.2 Zinc Homeostasis and the Immune System

13.3 Types of Zinc Signals

13.4 Zinc Signal and the Innate Immunity

13.5 Zinc Signal and the Adaptive Immunity

References

Chapter 14: Zinc Signals in Inflammation

14.1 Introduction

14.2 Zinc Signals and Inflammation

14.2.1 Zinc Signals

14.2.2 Zinc Homeostasis and Signaling Pathways

14.2.2.1 Zinc and the MAPK Pathway

14.2.2.2 Zinc and the NF?B Pathway

14.2.2.3 Zinc and GPCRs

14.2.2.4 Zinc and Other Signaling Pathways

14.2.2.5 Zinc and ROS

14.2.3 Zinc Signals in Acute Inflammation

14.2.3.1 Zinc and the Common Cold

14.2.3.2 Zinc and Sepsis

14.2.4 Zinc Signals in Chronic Inflammation

14.2.4.1 Zinc and Allergic Airway Inflammation

14.2.4.2 Zinc and Gastrointestinal (GI) Disorders

14.2.4.3 Zinc and Inflamm-Aging

14.3 Altered Zinc Homeostasis and Immune Cell Signaling in Inflammation

14.3.1 Zinc Signals and the Innate Immune System

14.3.1.1 Monocyte/Macrophages

14.3.1.2 Dendritic Cells

14.3.1.3 Neutrophils

14.3.1.4 Mast Cells

14.3.2 Zinc Signals and the Adaptive Immune System

14.3.2.1 T-Lymphocytes

14.3.2.2 B-Lymphocytes

14.4 Zinc Toxicity

14.5 Conclusions

References

Chapter 15: Zinc Transporters and Zinc Signaling in Skin Formation and Diseases

15.1 Zinc Transporters and Zinc Signaling

15.2 ZIP1

15.3 ZIP2

15.4 ZIP4

15.5 ZIP7

15.6 ZIP10

15.7 ZIP13

15.8 Other ZIP Family Members

15.9 Conclusion

References

Chapter 16: Post-translational Mechanisms of Zinc Signalling in Cancer

16.1 Introduction

16.2 Control of Intracellular Zinc Level

16.3 Classification and Predicted Membrane Topology of Zinc Transport Proteins

16.3.1 ZIP Channels

16.3.2 ZnT Transporters

16.4 Zinc and Cancer

16.5 ZIP Channels in Breast Cancer

16.5.1 ZIP7 in Breast Cancer

16.5.2 ZIP6 in Breast Cancer

16.5.3 ZIP10 in Breast Cancer

16.6 Zinc Signalling in Prostate Cancer

16.7 Post-translational Modifications of ZIP Channels

16.7.1 Phosphorylation

16.7.2 Proteolytic Cleavage of ZIP Channels

16.8 Conclusions

References

Chapter 17: Zinc Signaling (Zinc’ing) in Intestinal Function

17.1 Introduction

17.2 The Role of Zinc in Intestinal Function

17.3 Zinc Transporters in the Digestive Tract

17.3.1 Transporters Responsible for Uptake

17.3.2 Transporters Responsible for Intracellular Zn2+ Homeostasis

17.4 Intestinal Function of ZnR/GPR39

17.5 Conclusions and Future Directions

References

Chapter 18: In Situ Imaging of Zinc with Synthetic Fluorescent Probes

18.1 Introduction

18.2 Fluorogenic Probes

18.2.1 Design Principles and Applications

18.2.2 Visualizing Zinc in Cells and Tissues

18.2.3 Limitations and Artifacts

18.3 Ratiometric Fluorescent Probes

18.4 Fluorescent Probes for Two-Photon Excitation Microscopy

18.4.1 Design Principles and Applications

18.4.2 Ratiometric Probes for Two-Photon Microscopy

18.5 Conclusions

References

Chapter 19: Zinc Signals in Biology

19.1 Introduction

19.2 Zinc Homeostasis and Signaling in Bacteria

19.3 Zinc Homeostasis in Bacteria

19.4 Zinc-Responsive Two-Component Signal Transduction Systems in Bacteria

19.5 Zinc Homeostasis and Signaling in Fungi

19.6 Zinc Signals and Homeostasis in Caenorhabditis elegans

19.7 Zinc Homeostasis and Signaling in Fish

19.8 Conclusions

References

Index