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CRAC channelopathies.
Pflugers Arch. 2010 Jul; 460(2):417-35.PA

Abstract

Store-operated Ca2+ entry (SOCE) is an important Ca2+ influx pathway in many non-excitable and some excitable cells. It is regulated by the filling state of intracellular Ca2+ stores, notably the endoplasmic reticulum (ER). Reduction in [Ca2+]ER results in activation of plasma membrane Ca2+ channels that mediate sustained Ca2+ influx which is required for many cell functions as well as refilling of Ca2+ stores. The Ca2+ release activated Ca2+ (CRAC) channel is the best characterized SOC channel with well-defined electrophysiological properties. In recent years, the molecular components of the CRAC channel, long mysterious, have been defined. ORAI1 (or CRACM1) acts as the pore-forming subunit of the CRAC channel in the plasma membrane. Stromal interaction molecule (STIM) 1 is localized in the ER, senses [Ca2+]ER, and activates the CRAC channel upon store depletion by binding to ORAI1. Both proteins are widely expressed in many tissues in both human and mouse consistent with the widespread prevalence of SOCE and CRAC channel currents in many cells types. CRAC channelopathies in human patients with mutations in STIM1 and ORAI1 are characterized by abolished CRAC channel currents, lack of SOCE and-clinically-immunodeficiency, congenital myopathy, and anhydrotic ectodermal dysplasia. This article reviews the role of ORAI and STIM proteins for SOCE and CRAC channel function in a variety of cell types and tissues and compares the phenotypes of ORAI1 and STIM1-deficient human patients and mice with targeted deletion of Orai and Stim genes.

Authors+Show Affiliations

Department of Pathology, New York University, Langone Medical Center, SRB314, New York, NY 10016, USA. feskes01@nyumc.org

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20111871

Citation

Feske, Stefan. "CRAC Channelopathies." Pflugers Archiv : European Journal of Physiology, vol. 460, no. 2, 2010, pp. 417-35.
Feske S. CRAC channelopathies. Pflugers Arch. 2010;460(2):417-35.
Feske, S. (2010). CRAC channelopathies. Pflugers Archiv : European Journal of Physiology, 460(2), 417-35. https://doi.org/10.1007/s00424-009-0777-5
Feske S. CRAC Channelopathies. Pflugers Arch. 2010;460(2):417-35. PubMed PMID: 20111871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CRAC channelopathies. A1 - Feske,Stefan, Y1 - 2010/01/29/ PY - 2009/11/24/received PY - 2009/12/15/accepted PY - 2010/1/30/entrez PY - 2010/1/30/pubmed PY - 2010/9/14/medline SP - 417 EP - 35 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch VL - 460 IS - 2 N2 - Store-operated Ca2+ entry (SOCE) is an important Ca2+ influx pathway in many non-excitable and some excitable cells. It is regulated by the filling state of intracellular Ca2+ stores, notably the endoplasmic reticulum (ER). Reduction in [Ca2+]ER results in activation of plasma membrane Ca2+ channels that mediate sustained Ca2+ influx which is required for many cell functions as well as refilling of Ca2+ stores. The Ca2+ release activated Ca2+ (CRAC) channel is the best characterized SOC channel with well-defined electrophysiological properties. In recent years, the molecular components of the CRAC channel, long mysterious, have been defined. ORAI1 (or CRACM1) acts as the pore-forming subunit of the CRAC channel in the plasma membrane. Stromal interaction molecule (STIM) 1 is localized in the ER, senses [Ca2+]ER, and activates the CRAC channel upon store depletion by binding to ORAI1. Both proteins are widely expressed in many tissues in both human and mouse consistent with the widespread prevalence of SOCE and CRAC channel currents in many cells types. CRAC channelopathies in human patients with mutations in STIM1 and ORAI1 are characterized by abolished CRAC channel currents, lack of SOCE and-clinically-immunodeficiency, congenital myopathy, and anhydrotic ectodermal dysplasia. This article reviews the role of ORAI and STIM proteins for SOCE and CRAC channel function in a variety of cell types and tissues and compares the phenotypes of ORAI1 and STIM1-deficient human patients and mice with targeted deletion of Orai and Stim genes. SN - 1432-2013 UR - https://www.unboundmedicine.com/medline/citation/20111871/CRAC_channelopathies_ L2 - https://dx.doi.org/10.1007/s00424-009-0777-5 DB - PRIME DP - Unbound Medicine ER -