Faculty Opinions recommendation of The calcium store sensor, STIM1, reciprocally controls Orai and CaV1.2 channels.

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. PMID: 20929813 Funding information This work was supported by: NHLBI NIH HHS, United States Grant ID: HL55426 NIAID NIH HHS, United States Grant ID: AI058173 NHLBI NIH HHS, United States Grant ID: R01 HL055426 NIAID NIH HHS, United States Grant ID: R01 AI058173