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The Calcium store-sensor, STIM1, reciprocally controls Orai1 and Cav1.2 channels

Wang, Youjun and Deng, Xiaoxiang and Mancarella, Salvatore and Hendron, Eunan and Eguchi, Satoru and Soboloff, Jonathan and Tang, Xiang D. and Gill, Donald L. (2010) The Calcium store-sensor, STIM1, reciprocally controls Orai1 and Cav1.2 channels. Science, 330 (6000). pp. 105-109. ISSN 0036-8075

Abstract

Calcium signals, pivotal in controlling cell function, can be generated by calcium entry channels activated by depolarization of plasma membrane voltage 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 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 Ca2+ Psignal generation in excitable and nonexcitable cells

Item Type: Article
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Additional Information: The first author (Youjun Wang) was funded by Novartis.
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/3778

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