Store-Operated CRAC Channels

Murali Prakriya*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

In many animal cells, store-operated Ca2+ release-activated Ca2+ (CRAC) channels are an essential route for Ca2+ entry controlling a wide range of fundamental cellular functions including gene expression, secretion and cell proliferation. In line with their critical role in regulating cellular Ca2+ signaling, CRAC channels are also involved in the etiology of several disease processes including a severe combined immunodeficiency syndrome. CRAC channels are distinguished by several unique biophysical and molecular features including exquisite Ca2+ selectivity, low unitary conductance, and store-operated gating, and are formed from the assembly of two essential molecules: the STIM proteins, which serve as the ER Ca2+ sensors, and the ORAI proteins, which form the channel pore. ER Ca2+ store depletion triggers interactions between the STIM sensors and ORAI channels driving their redistribution and accumulation into overlapping puncta at peripheral cellular sites to elicit localized elevations of [Ca2+]i at clusters of CRAC channels. This chapter examines the molecular features of the STIM and ORAI proteins that regulate the operation of CRAC channels and highlights key physiological roles in select organ systems.

Original languageEnglish (US)
Title of host publicationTextbook of Ion Channels Volume II
Subtitle of host publicationProperties, Function, and Pharmacology of the Superfamilies
PublisherCRC Press
Pages387-400
Number of pages14
ISBN (Electronic)9781000857740
ISBN (Print)9780367538163
DOIs
StatePublished - Jan 1 2023

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Neuroscience
  • General Medicine

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