The calcium store sensor, STIM1, reciprocally controls Orai and Ca V1.2 channels

Youjun Wang, Xiaoxiang Deng, Salvatore Mancarella, Eunan Hendron, Satoru Eguchi, Jonathan Soboloff, Xiang D. Tang, Donald L. Gill

Research output: Contribution to journalArticle

242 Scopus citations

Abstract

Calcium signals, pivotal in controlling cell function, can be generated by calcium entry channels activated by plasma membrane depolarization or depletion of internal calcium stores. We reveal a regulatory link between these two channel subtypes mediated by the ubiquitous calcium-sensing STIM proteins. STIM1 activation by store depletion or mutational modification strongly suppresses voltage-operated calcium (CaV1.2) channels while activating store-operated Orai channels. Both actions are mediated by the short STIM-Orai activating region (SOAR) of STIM1. STIM1 interacts with CaV1.2 channels and localizes within discrete endoplasmic reticulum/plasma membrane junctions containing both CaV1.2 and Orai1 channels. Hence, STIM1 interacts with and reciprocally controls two major calcium channels hitherto thought to operate independently. Such coordinated control of the widely expressed CaV1.2 and Orai channels has major implications for Ca 2+ signal generation in excitable and nonexcitable cells.

Original languageEnglish (US)
Pages (from-to)105-109
Number of pages5
JournalScience
Volume330
Issue number6000
DOIs
StatePublished - Oct 1 2010

All Science Journal Classification (ASJC) codes

  • General

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    Wang, Y., Deng, X., Mancarella, S., Hendron, E., Eguchi, S., Soboloff, J., Tang, X. D., & Gill, D. L. (2010). The calcium store sensor, STIM1, reciprocally controls Orai and Ca V1.2 channels. Science, 330(6000), 105-109. https://doi.org/10.1126/science.1191086