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Science 330 (6000): 105-109

Copyright © 2010 by the American Association for the Advancement of Science

The Calcium Store Sensor, STIM1, Reciprocally Controls Orai and CaV1.2 Channels

Youjun Wang,1 Xiaoxiang Deng,1,* Salvatore Mancarella,1,* Eunan Hendron,1,* Satoru Eguchi,2 Jonathan Soboloff,1 Xiang D. Tang,3 Donald L. Gill1,{dagger}

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 Ca2+ signal generation in excitable and nonexcitable cells.

1 Department of Biochemistry and Cardiovascular Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
2 Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
3 Department of Pharmacology, Nankai University School of Medicine, Tianjin 300071, China.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dgill{at}temple.edu

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