Store-Operated Calcium Entry Mediated by ORAI and STIM.
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The calcium release-activated calcium (CRAC) channel, composed of ORAI and stromal interaction molecules (STIM), represents a prototypical example of store-operated calcium entry in mammals. The ORAI-STIM signaling occurs at membrane contact sites formed by close appositions between the endoplasmic reticulum (ER) and the plasma membrane. ORAI1 is a four-pass transmembrane protein that forms a highly calcium-selective ion channel in the plasma membrane. STIM1 is an ER-resident, a single-pass transmembrane protein that serves as a calcium sensor within the ER lumen and a potent activator of ORAI1 calcium channels. The intricate interplay between ORAI and STIM controls calcium entry into cells to regulate a myriad of physiological processes. We highlight herein the current knowledge on the structure-function relationship of CRAC channel, with a focus on key structural elements that mediate STIM1 conformational switch and the dynamic coupling between STIM1 and ORAI1. Furthermore, we discuss the physiological roles of STIM-ORAI signaling in various tissues and organs, as well as major pathological conditions arising from loss- or gain-of-function mutations in human ORAI1 and STIM1. © 2017 American Physiological Society. Compr Physiol 8:981-1002, 2018.
author list (cited authors)
Nguyen, N. T., Han, W., Cao, W., Wang, Y., Wen, S., Huang, Y., ... Zhou, Y.
complete list of authors
Nguyen, Nhung T||Han, Weidong||Cao, Wen-Ming||Wang, Youjun||Wen, Shufan||Huang, Yun||Li, Minyong||Du, Lupei||Zhou, Yubin