Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx - Evidence for similarities in store-operated and calcium release-activated calcium channel components
Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx - Evidence for similarities in store-operated and calcium release-activated calcium channel components
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DOI：
10.1074/jbc.m608942200
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发表时间：
2007-03-23
影响因子：
4.8
通讯作者：
Ambudkar, Indu S.
中科院分区：
文献类型：
--
作者：
Ong, Hwei Ling;Cheng, Kwong Tai;Ambudkar, Indu S.
钙池操纵的钙内流（Store-operated calcium entry，SOCE）是一种普遍存在的机制，由不同的SOC通道介导，从大鼠嗜碱性白血病和其他造血细胞中的高选择性钙释放激活的Ca 2+（CRAG）通道到其他细胞中的相对Ca 2+选择性或非选择性SOC通道。虽然这些通道的确切组成尚未确定，但TRPC 1有助于SOC通道和调节各种细胞类型的生理功能。最近，Orai 1和STIM 1已被认为足以生成CRAC通道。在这里，我们表明，Orai 1和STIM 1也需要TRPC 1-SOC通道。TRPC 1，Orai 1或STIM 1的敲低减弱，而TRPC 1的过表达，而不是Orai 1或STIM 1，诱导SOC进入和I-SOC在人唾液腺细胞中的增加。所有这三种蛋白质共定位于细胞的质膜区域，毒胡萝卜素增加TRPC 1与STIM 1和Orai 1在人唾液腺细胞以及分散的小鼠颌下腺细胞中的免疫共沉淀。总的来说，这里提供的数据表明，所有三种蛋白质是必不可少的在这些细胞中的I-SOC的产生和TRPC 1-STIM 1-Orai 1三元复合物的动态组装参与SOC通道的激活响应内部Ca 2+存储耗尽。因此，这些数据表明SOC和CRAC通道具有共同的分子基础。
Store-operated calcium entry (SOCE) is a ubiquitous mechanism that is mediated by distinct SOC channels, ranging from the highly selective calcium release-activated Ca2+ (CRAG) channel in rat basophilic leukemia and other hematopoietic cells to relatively Ca2+-selective or non-selective SOC channels in other cells. Although the exact composition of these channels is not yet established, TRPC1 contributes to SOC channels and regulation of physiological function of a variety of cell types. Recently, Orai1 and STIM1 have been suggested to be sufficient for generating CRAC channels. Here we show that Orai1 and STIM1 are also required for TRPC1-SOC channels. Knockdown of TRPC1, Orai1, or STIM1 attenuated, whereas overexpression of TRPC1, but not Orai1 or STIM1, induced an increase in SOC entry and I-SOC in human salivary gland cells. All three proteins were co-localized in the plasma membrane region of cells, and thapsigargin increased co-immunoprecipitation of TRPC1 with STIM1, and Orai1 in human salivary gland cells as well as dispersed mouse submandibular gland cells. In aggregate, the data presented here reveal that all three proteins are essential for generation of I-SOC in these cells and that dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in activation of SOC channel in response to internal Ca2+ store depletion. Thus, these data suggest a common molecular basis for SOC and CRAC channels.