Store-operated calcium channels

Murali Prakriya, Richard S. Lewis*

*Corresponding author for this work

Research output: Contribution to journalArticle

424 Scopus citations

Abstract

Store-operated cofor calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca2+ from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca2+ sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca2+ from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca2+ depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease.

Original languageEnglish (US)
Pages (from-to)1383-1436
Number of pages54
JournalPhysiological Reviews
Volume95
Issue number4
DOIs
StatePublished - Sep 23 2015

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Store-operated calcium channels'. Together they form a unique fingerprint.

  • Cite this