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CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs.
Cell Calcium. 2019 06; 80:112-116.CC

Abstract

Ca2+ release-activated Ca2+ (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic analysis of patients with abolished CRAC channel function. And patients with autosomal recessive loss-of-function (LOF) mutations in ORAI1 and its activator stromal interaction molecule 1 (STIM1) that abolish CRAC channel function and store-operated Ca2+ entry (SOCE) define essential functions of CRAC channels in health and disease. Conversely, gain-of-function (GOF) mutations in ORAI1 and STIM1 are associated with tubular aggregate myopathy (TAM) and Stormorken syndrome due to constitutive CRAC channel activation. In addition, genetically engineered animal models of ORAI and STIM function have provided important insights into the physiological and pathophysiological roles of CRAC channels in cell types and organs beyond those affected in human patients. The picture emerging from this body of work shows CRAC channels as important regulators of cell function in many tissues, and as potential drug targets for the treatment of autoimmune and inflammatory disorders.

Authors+Show Affiliations

Department of Pathology, New York University School of Medicine, New York, NY, 10016, USA. Electronic address: 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

31009822

Citation

Feske, Stefan. "CRAC Channels and Disease - From Human CRAC Channelopathies and Animal Models to Novel Drugs." Cell Calcium, vol. 80, 2019, pp. 112-116.
Feske S. CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs. Cell Calcium. 2019;80:112-116.
Feske, S. (2019). CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs. Cell Calcium, 80, 112-116. https://doi.org/10.1016/j.ceca.2019.03.004
Feske S. CRAC Channels and Disease - From Human CRAC Channelopathies and Animal Models to Novel Drugs. Cell Calcium. 2019;80:112-116. PubMed PMID: 31009822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs. A1 - Feske,Stefan, Y1 - 2019/03/11/ PY - 2019/03/09/received PY - 2019/03/09/accepted PY - 2019/4/23/pubmed PY - 2020/7/28/medline PY - 2019/4/23/entrez KW - CRAC channel KW - Calcium KW - Disease KW - Immunodeficiency KW - Mutation KW - ORAI1 KW - STIM1 SP - 112 EP - 116 JF - Cell calcium JO - Cell Calcium VL - 80 N2 - Ca2+ release-activated Ca2+ (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic analysis of patients with abolished CRAC channel function. And patients with autosomal recessive loss-of-function (LOF) mutations in ORAI1 and its activator stromal interaction molecule 1 (STIM1) that abolish CRAC channel function and store-operated Ca2+ entry (SOCE) define essential functions of CRAC channels in health and disease. Conversely, gain-of-function (GOF) mutations in ORAI1 and STIM1 are associated with tubular aggregate myopathy (TAM) and Stormorken syndrome due to constitutive CRAC channel activation. In addition, genetically engineered animal models of ORAI and STIM function have provided important insights into the physiological and pathophysiological roles of CRAC channels in cell types and organs beyond those affected in human patients. The picture emerging from this body of work shows CRAC channels as important regulators of cell function in many tissues, and as potential drug targets for the treatment of autoimmune and inflammatory disorders. SN - 1532-1991 UR - https://www.unboundmedicine.com/medline/citation/31009822/CRAC_channels_and_disease___From_human_CRAC_channelopathies_and_animal_models_to_novel_drugs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4160(19)30047-8 DB - PRIME DP - Unbound Medicine ER -