↓ Skip to main content

Store-Operated Ca²⁺ Entry (SOCE) Pathways

Overview of attention for book
Cover of 'Store-Operated Ca²⁺ Entry (SOCE) Pathways'

Table of Contents

  1. Altmetric Badge
    Book Overview
  2. Altmetric Badge
    Chapter 1 Introduction
  3. Altmetric Badge
    Chapter 2 The STIM-Orai Pathway: STIM-Orai Structures: Isolated and in Complex
  4. Altmetric Badge
    Chapter 3 The STIM-Orai Pathway: Orai, the Pore-Forming Subunit of the CRAC Channel
  5. Altmetric Badge
    Chapter 4 The STIM-Orai Pathway: The Interactions Between STIM and Orai
  6. Altmetric Badge
    Chapter 5 The STIM-Orai Pathway: Conformational Coupling Between STIM and Orai in the Activation of Store-Operated Ca2+ Entry
  7. Altmetric Badge
    Chapter 6 The STIM-Orai Pathway: Regulation of STIM and Orai by Thiol Modifications
  8. Altmetric Badge
    Chapter 7 The STIM-Orai Pathway: Light-Operated Ca2+ Entry Through Engineered CRAC Channels
  9. Altmetric Badge
    Chapter 8 STIM-TRP Pathways and Microdomain Organization: Ca2+ Influx Channels: The Orai-STIM1-TRPC Complexes
  10. Altmetric Badge
    Chapter 9 STIM-TRP Pathways and Microdomain Organization: Contribution of TRPC1 in Store-Operated Ca2+ Entry: Impact on Ca2+ Signaling and Cell Function
  11. Altmetric Badge
    Chapter 10 STIM-TRP Pathways and Microdomain Organization: Auxiliary Proteins of the STIM/Orai Complex
  12. Altmetric Badge
    Chapter 11 Introduction
  13. Altmetric Badge
    Chapter 12 New Aspects of the Contribution of ER to SOCE Regulation: The Role of the ER and ER-Plasma Membrane Junctions in the Regulation of SOCE
  14. Altmetric Badge
    Chapter 13 New Aspects of the Contribution of ER to SOCE Regulation: TRPC Proteins as a Link Between Plasma Membrane Ion Transport and Intracellular Ca2+ Stores
  15. Altmetric Badge
    Chapter 14 The Role of Mitochondria in the Activation/Maintenance of SOCE: Store-Operated Ca2+ Entry and Mitochondria
  16. Altmetric Badge
    Chapter 15 The Role of Mitochondria in the Activation/Maintenance of SOCE: Membrane Contact Sites as Signaling Hubs Sustaining Store-Operated Ca2+ Entry
  17. Altmetric Badge
    Chapter 16 The Role of Mitochondria in the Activation/Maintenance of SOCE: The Contribution of Mitochondrial Ca2+ Uptake, Mitochondrial Motility, and Location to Store-Operated Ca2+ Entry
  18. Altmetric Badge
    Chapter 17 Tissue Specificity: The Role of Organellar Membrane Nanojunctions in Smooth Muscle Ca2+ Signaling
  19. Altmetric Badge
    Chapter 18 Tissue Specificity: SOCE: Implications for Ca2+ Handling in Endothelial Cells
  20. Altmetric Badge
    Chapter 19 Tissue Specificity: Store-Operated Ca2+ Entry in Cardiac Myocytes
  21. Altmetric Badge
    Chapter 20 Introduction: Overview of the Pathophysiological Implications of Store-Operated Calcium Entry in Mammalian Cells
  22. Altmetric Badge
    Chapter 21 Immunological Disorders: Regulation of Ca2+ Signaling in T Lymphocytes
  23. Altmetric Badge
    Chapter 22 Cardiovascular and Hemostatic Disorders: Role of STIM and Orai Proteins in Vascular Disorders
  24. Altmetric Badge
    Chapter 23 Cardiovascular and Hemostatic Disorders: SOCE and Ca2+ Handling in Platelet Dysfunction
  25. Altmetric Badge
    Chapter 24 Cardiovascular and Hemostatic Disorders: SOCE in Cardiovascular Cells: Emerging Targets for Therapeutic Intervention
  26. Altmetric Badge
    Chapter 25 Cardiac Remodeling and Disease: SOCE and TRPC Signaling in Cardiac Pathology
  27. Altmetric Badge
    Chapter 26 Cardiac Remodeling and Disease: Current Understanding of STIM1/Orai1-Mediated Store-Operated Ca2+ Entry in Cardiac Function and Pathology
  28. Altmetric Badge
    Chapter 27 Neurological and Motor Disorders: Neuronal Store-Operated Ca2+ Signaling: An Overview and Its Function
  29. Altmetric Badge
    Chapter 28 Neurological and Motor Disorders: TRPC in the Skeletal Muscle
  30. Altmetric Badge
    Chapter 29 Fertility: Store-Operated Ca2+ Entry in Germ Cells: Role in Egg Activation
  31. Altmetric Badge
    Chapter 30 Metabolic Disorders and Cancer: Hepatocyte Store-Operated Ca2+ Channels in Nonalcoholic Fatty Liver Disease
  32. Altmetric Badge
    Chapter 31 Metabolic Disorders and Cancer: Store-Operated Ca2+ Entry in Cancer: Focus on IP3R-Mediated Ca2+ Release from Intracellular Stores and Its Role in Migration and Invasion
Attention for Chapter 5: The STIM-Orai Pathway: Conformational Coupling Between STIM and Orai in the Activation of Store-Operated Ca2+ Entry
Altmetric Badge

Citations

dimensions_citation
3 Dimensions

Readers on

mendeley
17 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Chapter title
The STIM-Orai Pathway: Conformational Coupling Between STIM and Orai in the Activation of Store-Operated Ca2+ Entry
Chapter number 5
Book title
Store-Operated Ca²⁺ Entry (SOCE) Pathways
Published in
Advances in experimental medicine and biology, January 2017
DOI 10.1007/978-3-319-57732-6_5
Pubmed ID
Book ISBNs
978-3-31-957731-9, 978-3-31-957732-6
Authors

Robert M. Nwokonko, Xiangyu Cai, Natalia A. Loktionova, Youjun Wang, Yandong Zhou, Donald L. Gill

Abstract

Store-operated Ca(2+) entry fulfills a crucial role in controlling Ca(2+) signals in almost all cells. The Ca(2+)-sensing stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER) undergo complex conformational changes in response to depleted ER luminal Ca(2+), allowing them to unfold and become trapped in ER-plasma membrane (PM) junctions. Dimers of STIM proteins trap and gate the plasma membrane Orai Ca(2+) channels within these junctions to generate discrete zones of high Ca(2+) and regulate sensitive Ca(2+)-dependent intracellular signaling pathways. The STIM-Orai activating region (SOAR) of STIM1 becomes exposed upon store depletion and promotes trapping of Orai1 at the PM. Residue Phe-394 within SOAR forms an integral part of the high-affinity Orai1-interacting site. Our results demonstrate that only a single active site within the dimeric SOAR domain of STIM1 is required for the activation of Orai1 channel activity. This unimolecular model is strongly supported by evidence of variable STIM1:Orai1 stoichiometry reported in many studies. We hypothesize that unimolecular coupling promotes cross-linking of channels, localizing Ca(2+) signals, and regulating channel activity. We have also identified a key "nexus" region in Orai1 near the C-terminal STIM1-binding site that can be mutated to constitutively activate Ca(2+) entry, mimicking STIM1 activated channels. This suggests that STIM1 mediates gating of Orai1 in an allosteric manner via interaction with the Orai1 C-terminus alone. This model suggests the dual role of STIM1 in regulating both localization and gating of Orai1 channels and has important implications for the regulation of SOCE-mediated downstream signaling and the kinetics of channel activation.

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 24%
Researcher 3 18%
Other 2 12%
Student > Master 2 12%
Professor 1 6%
Other 2 12%
Unknown 3 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 29%
Agricultural and Biological Sciences 4 24%
Veterinary Science and Veterinary Medicine 1 6%
Mathematics 1 6%
Pharmacology, Toxicology and Pharmaceutical Science 1 6%
Other 1 6%
Unknown 4 24%