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

被引：265

作者：

Park, Chan Young ^{[1
,2
]}

Shcheglovitov, Aleksandr ^{[1
]}

Dolmetsch, Ricardo ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA

[2] UNIST, Sch Nanobiotechnol & Chem Engn, Ulsan 689798, South Korea

来源：

SCIENCE | 2010年 / 330卷 / 6000期

关键词：

MEDIUM SPINY NEURONS; T-LYMPHOCYTES; SKELETAL-MUSCLE; PLASMA-MEMBRANE; CA2+ CHANNELS; STORE; ENTRY; ORAI1; INFLUX; SENSOR;

D O I：

10.1126/science.1191027

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 Ca(V)1.2. STIM1 binds to the C terminus of Ca(V)1.2 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.

引用

页码：101 / 105

页数：5

共 29 条

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