期刊
ANNUAL REVIEW OF IMMUNOLOGY, VOL 28
卷 28, 期 -, 页码 491-533出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev.immunol.021908.132550
关键词
CRAC channels; store-operated calcium entry; T cell activation; primary immunodeficiencies
类别
资金
- NIAID NIH HHS [R01 AI084167, R01 AI084167-06, R01 AI040127-15, R01 AI040127] Funding Source: Medline
- NIDA NIH HHS [RC1 DA028422, RC1 DA028422-01] Funding Source: Medline
- NIGMS NIH HHS [R01 GM045374] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI084167, R01AI040127] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM045374] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [RC1DA028422] Funding Source: NIH RePORTER
Ca2+ entry into cells of the peripheral immune system occurs through highly Ca2+-selective channels known as CRAC (calcium release-activated calcium) channels. CRAG channels are a very well-characterized example of store-operated Ca2+ channels, so designated because they open when the endoplasmic reticulum (ER) Ca2+ store becomes depleted. Physiologically, Ca2+ is released from the ER lumen into the cytoplasm when activated receptors couple to phospholipase C and trigger production of the second messenger inositol 1,4,5-trisphosphate (IP3). IP3 binds to IP3 receptors in the ER membrane and activates Ca2+ release. The proteins STIM and ORAI were discovered through limited and genome-wide RNAi screens, respectively, performed in Drosophila cells and focused on identifying modulators of store-operated Ca2+ entry. STIM1 and STIM2 sense the depletion of ER Ca2+ stores, whereas ORAI1 is a pore subunit of the CRAG channel. In this review, we discuss selected aspects of Ca2+ signaling in cells of the immune system, focusing on the roles of STIM and ORAI proteins in store-operated Ca2+ entry.
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