The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels |
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Authors: | Wang Youjun Deng Xiaoxiang Mancarella Salvatore Hendron Eunan Eguchi Satoru Soboloff Jonathan Tang Xiang D Gill Donald L |
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Institution: | Department of Biochemistry and Cardiovascular Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA. |
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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 (Ca(V)1.2) channels while activating store-operated Orai channels. Both actions are mediated by the short STIM-Orai activating region (SOAR) of STIM1. STIM1 interacts with Ca(V)1.2 channels and localizes within discrete endoplasmic reticulum/plasma membrane junctions containing both Ca(V)1.2 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 Ca(V)1.2 and Orai channels has major implications for Ca(2+) signal generation in excitable and nonexcitable cells. |
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