Orais and STIMs: physiological mechanisms and disease

Journal of Cellular and Molecular Medicine

A. Berna-Erro²  G. E. Woodard¹ 

[1] National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA;Department of Physiology, University of Extremadura, Cáceres, Spain

关键词: STIM;    Orai;    store‐operated Ca2+ entry;    CRAC;    immunodeficiency;   

DOI  :  10.1111/j.1582-4934.2011.01395.x

来源: Wiley

【 摘 要 】

Abstract

• • Introduction
• • Intracellular Ca²⁺ stores and disease
•     -   Mechanisms of intracellular Ca²⁺ homeostasis
•     -   Abnormal intracellular Ca²⁺ homeostasis and disease
• • Sensing Ca²⁺ stores
• • Importance of Orais and STIMs in tissues
• • Participation of Orai and STIM in human diseases
•     -   Orai1-deficient function and human disease
•     -   STIM1-deficient function and human disease
•     -   Orai1 and STIM1 in human diabetic platelets
• • Orai and STIM mutant mouse as models of disease
•     -   Sudden and perinatal mortality
•     -   Immunodeficiency
•     -   Autoimmune and inflammatory diseases
•     -   Skeletal muscle
•     -   Thrombosis and haemostasis
•     -   Neuronal system
• • Emerging studies of Orai and STIM in cancer    and cell cycle
• • Concluding remarks

The stromal interaction molecules STIM1 and STIM2 are Ca²⁺ sensors, mostly located in the endoplasmic reticulum, that detect changes in the intraluminal Ca²⁺ concentration and communicate this information to plasma membrane store-operated channels, including members of the Orai family, thus mediating store-operated Ca²⁺ entry (SOCE). Orai and STIM proteins are almost ubiquitously expressed in human cells, where SOCE has been reported to play a relevant functional role. The phenotype of patients bearing mutations in STIM and Orai proteins, together with models of STIM or Orai deficiency in mice, as well as other organisms such as Drosophila melanogaster, have provided compelling evidence on the relevant role of these proteins in cellular physiology and pathology. Orai1-deficient patients suffer from severe immunodeficiency, congenital myopathy, chronic pulmonary disease, anhydrotic ectodermal dysplasia and defective dental enamel calcification. STIM1-deficient patients showed similar abnormalities, as well as autoimmune disorders. This review summarizes the current evidence that identifies and explains diseases induced by disturbances in SOCE due to deficiencies or mutations in Orai and STIM proteins.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd