SARAF Inactivates the Store Operated Calcium Entry Machinery to Prevent Excess Calcium Refilling
SARAF Inactivates the Store Operated Calcium Entry Machinery to Prevent Excess Calcium Refilling
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DOI：
10.1016/j.cell.2012.01.055
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发表时间：
2012-04-13
期刊：
影响因子：
64.5
通讯作者：
Reuveny, Eitan
中科院分区：
文献类型：
--
作者：
Palty, Raz;Raveh, Adi;Reuveny, Eitan
钙库操作性钙内流（SOCE）是细胞调节基础钙、补充细胞内钙库并执行广泛的专门活动的主要细胞过程。STIM和奥赖蛋白已被鉴定为能够重建介导SOCE的Ca 2+释放激活的Ca 2+（CRAC）通道的基本组分。在这里，我们报告的分子鉴定SARAF作为负调节SOCE。使用异源表达，RNAi介导的沉默和定点诱变结合电生理，生物化学和成像技术，我们表明，SARAF是一种内质网膜驻留蛋白，与STIM，以促进缓慢的钙依赖性失活的SOCE。SARAF在塑造胞质Ca 2+信号和确定主要细胞内Ca 2+储存的含量方面起着关键作用，这一作用在保护细胞免受Ca 2+过度填充方面可能很重要。
Store operated calcium entry (SOCE) is a principal cellular process by which cells regulate basal calcium, refill intracellular Ca2+ stores, and execute a wide range of specialized activities. STIM and Orai proteins have been identified as the essential components enabling the reconstitution of Ca2+ release-activated Ca2+ (CRAC) channels that mediate SOCE. Here, we report the molecular identification of SARAF as a negative regulator of SOCE. Using heterologous expression, RNAi-mediated silencing and site directed mutagenesis combined with electrophysiological, biochemical and imaging techniques we show that SARAF is an endoplasmic reticulum membrane resident protein that associates with STIM to facilitate slow Ca2+-dependent inactivation of SOCE. SARAF plays a key role in shaping cytosolic Ca2+ signals and determining the content of the major intracellular Ca2+ stores, a role that is likely to be important in protecting cells from Ca2+ overfilling.