STIM1, an essential and conserved component of store-operated Ca2+ channel function.
STIM1, an essential and conserved component of store-operated Ca2+ channel function.
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Stim1，是存储经营的Ca2+通道函数的必不可少的组件。
DOI：
10.1083/jcb.200502019
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发表时间：
2005-05-09
影响因子：
7.8
通讯作者：
Stauderman, Kenneth A
中科院分区：
文献类型：
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作者：
Roos, Jack;DiGregorio, Paul J;Yeromin, Andriy V;Ohlsen, Kari;Lioudyno, Maria;Zhang, Shenyuan;Safrina, Olga;Kozak, J Ashot;Wagner, Steven L;Cahalan, Michael D;Velicelebi, Gonul;Stauderman, Kenneth A
储存操作的Ca2+ (SOC)通道调节许多细胞过程，但潜在的分子成分尚未很好地定义。使用基于RNA干扰（RNAi）的筛选来鉴定改变thapsignargin （TG）依赖性Ca2+进入的基因，我们发现了Stim在SOC内流中必需和保守的作用。果蝇S2细胞中rnai介导的Stim敲低显著减少tg依赖性Ca2+进入。膜片钳记录显示果蝇Ca2+释放激活的Ca2+ (CRAC)电流几乎完全被抑制，该电流具有与人类T细胞中CRAC电流相似的生物物理特征。同样，敲低人类同源STIM1显著降低Jurkat T细胞中的CRAC通道活性。rnai介导的STIM1敲低抑制TG或激动剂依赖性Ca2+进入HEK293或SH-SY5Y细胞。相反，HEK293细胞中STIM1的过表达适度增强了tg诱导的Ca2+进入。我们认为STIM1是一种从果蝇到哺乳动物细胞普遍表达的蛋白，在SOC内流中起重要作用，可能是SOC和CRAC通道的共同组成部分。
Store-operated Ca2+ (SOC) channels regulate many cellular processes, but the underlying molecular components are not well defined. Using an RNA interference (RNAi)-based screen to identify genes that alter thapsigargin (TG)-dependent Ca2+ entry, we discovered a required and conserved role of Stim in SOC influx. RNAi-mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG-dependent Ca2+ entry. Patch-clamp recording revealed nearly complete suppression of the Drosophila Ca2+ release-activated Ca2+ (CRAC) current that has biophysical characteristics similar to CRAC current in human T cells. Similarly, knockdown of the human homologue STIM1 significantly reduced CRAC channel activity in Jurkat T cells. RNAi-mediated knockdown of STIM1 inhibited TG- or agonist-dependent Ca2+ entry in HEK293 or SH-SY5Y cells. Conversely, overexpression of STIM1 in HEK293 cells modestly enhanced TG-induced Ca2+ entry. We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels.