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Science 330 (6000): 101-105

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

The CRAC Channel Activator STIM1 Binds and Inhibits L-Type Voltage-Gated Calcium Channels

Chan Young Park,1,2 Aleksandr Shcheglovitov,1 Ricardo Dolmetsch1,*

Abstract: Voltage- and store-operated calcium (Ca2+) channels are the major routes of Ca2+ entry in mammalian cells, but little is known about how cells coordinate the activity of these channels to generate coherent calcium signals. We found that STIM1 (stromal interaction molecule 1), the main activator of store-operated Ca2+ channels, directly suppresses depolarization-induced opening of the voltage-gated Ca2+ channel CaV1.2. STIM1 binds to the C terminus of CaV1.2 through its Ca2+ release–activated Ca2+ activation domain, acutely inhibits gating, and causes long-term internalization of the channel from the membrane. This establishes a previously unknown function for STIM1 and provides a molecular mechanism to explain the reciprocal regulation of these two channels in cells.

1 Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2 School of Nano-Biotechnology and Chemical Engineering, UNIST, Banyeon-ri 100, Ulsan 689-798, Republic of Korea.

* To whom correspondence should be addressed. E-mail: ricardo.dolmetsch{at}stanford.edu


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