Store-Operated Calcium Channels

Chapter One. Store-Operated Orai Channels: Structure and Function

1 Introduction

2 Identification of the Orai Proteins

3 STIM1 Is the ER Ca^2 + Sensor for SOCE

4 Orai1 Is the Pore-Forming Subunit of the CRAC Channel

5 The CRAC Channel Is Essential for Lymphocyte Activation

6 Oligomerization and Redistribution of STIM1 to the ER–Plasma Membrane Junctions

7 Conformational Changes in STIM1

8 STIM1 Directly Binds to Orai1

9 Orai1 Domains Involved in STIM1 Binding

10 CRAC Channel Subunit Stoichiometry

11 How Many STIM Molecules Does It Take to Activate CRAC Channels?

12 Structural Basis of Selectivity and Permeation

13 STIM1 Regulates CRAC Channel Ion Selectivity

14 Regulation of CRAC Channels by Calcium

15 Conclusions

Acknowledgments

References

Chapter Two. STIM–ORAI Interactions That Control the CRAC Channel

1 Overview of STIM–ORAI Interactions

2 The C-terminal Region of the ORAI Channel

3 The N-terminal Region of the ORAI Channel

4 Conclusion

Acknowledgments

References

Chapter Three. Structure and Function of Endoplasmic Reticulum STIM Calcium Sensors

1 Introduction

2 STIM and Orai Domain Architectures

3 STIM1 and Orai1 in the Activation in SOCE

4 Human STIM1 and STIM2 EF–SAM Biophysical Features

5 Human STIM1 EF–SAM Structure

6 Human STIM2 EF–SAM Structure

7 Human STIM1 and STIM2 Cytosolic Domains

8 STIM Coupling to Orai

9 Concluding Remarks

Acknowledgments

References

Chapter Four. On the Stoichiometry of Resting and Activated CRAC Channels

1 The Stoichiometry of Orai1

2 The Stoichiometry of STIM1

3 Summary

Acknowledgments

References

Chapter Five. Alternative Forms of the Store-Operated Calcium Entry Mediators, STIM1 and Orai1

1 Store-Operated Channels

2 STIM1 Phosphorylation in Mitosis

3 Two Forms of Orai1

4 Summary and Remaining Questions

Acknowledgment

References

Chapter Six. The ARC Channel—An Endogenous Store-Independent Orai Channel

1 Introduction

2 Store-Independent Calcium Entry and the Discovery of the ARC Channels

3 Molecular Identity of the ARC Channel

4 Molecular Basis of ARC Channel Activation

5 Regulation of ARC Channel Activity

6 What Do ARC Channels Do?

7 Speculations and Conclusions

Acknowledgment

References

Chapter Seven. Contribution and Regulation of TRPC Channels in Store-Operated Ca^2 + Entry

1 Introduction

2 Physiological Functions of TRPC Channel-Mediated SOCE

3 Characteristics of TRPC Channels

4 TRPC1 Channel in SOCE

5 Plasma Membrane Domains Involved in SOCE

6 Distinct Physiological Functions of TRPC1 and Orai1

7 Assembly and Function of TRPC/STIM1/Orai1 Microdomains

8 Conclusion

References

Chapter Eight. Molecular Regulation of the Pore Component of CRAC Channels, Orai1

1 Introduction

2 Current Understanding of CRAC Channel Activation and Inactivation

3 Cytoplasmic Ca^2 +-Sensitive Interactors of CRAC Channels—CaM and CRACR2A

4 Negative Regulators of Orai1-Mediated SOCE

5 Positive Regulators of Orai1-Mediated SOCE

6 Adenylate Cyclase-Mediated Cross Talk Between cAMP and Ca^2 + Signaling Pathway

7 Orai Proteins and ARC Channels

8 Posttranslational Modification of CRAC Channel Components

9 Relationship Between Mitochondria and SOCE

10 Conclusions

Acknowledgments

References

Chapter Nine. Emerging Roles for Native Orai Ca²⁺ Channels in Cardiovascular Disease

1 Introduction

2 Orai Channels

3 Orai Channels in the Heart

4 Orai Channels in Vessels

5 Conclusion and Perspective

Acknowledgments

References

Chapter Ten. The Neglected CRAC Proteins: Orai2, Orai3, and STIM2

1 Introduction

2 STIM2

3 Orai2

4 Orai3

5 Outlook and Open Questions

Acknowledgments

References

Index