Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels
Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels
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DOI：
10.1126/science.287.5458.1647
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发表时间：
2000-03-03
期刊：
影响因子：
56.9
通讯作者：
Gill, DL
中科院分区：
文献类型：
--
作者：
Ma, HT;Patterson, RL;Gill, DL
内质网(ER)、钙离子(Ca~(2+))存储和质膜(PM)存储操作通道(SOCs)之间的耦合机制对Ca~(2+)信号转导至关重要，但一直未能被检测到。SOCs可能在功能上与受体操作的Trp家族有关。在人胚胎肾(HEK293)细胞中，内源性SOC与稳定表达的TRP3通道的直接比较表明，TRP3通道不同于存储非依赖性。然而，浓缩的皮质F-肌动蛋白阻止了SOC和TRP3通道的激活，这表明ER-PM相互作用是这两种通道耦合的基础。三磷酸肌醇受体(INSP(2)R)的细胞活性抑制剂2-氨基乙氧基二苯基苯酯可同时阻止受体诱导的TRP3激活和受体诱导的SOC激活。结论：Insp(3)Rs同时调节SOC和Trp通道的开放，并且Insp(3)Rs对于维持SOC的排空和生理激活之间的耦合是必要的。
The coupling mechanism between endoplasmic reticulum (ER) calcium ion (Ca2+) stores and plasma membrane (PM) store-operated channels (SOCs) is crucial to Ca2+ signaling but has eluded detection. SOCs may be functionally related to the TRP family of receptor-operated channels. Direct comparison of endogenous SOCs with stably expressed TRP3 channels in human embryonic kidney (HEK293) cells revealed that TRP3 channels differ in being store independent. However, condensed cortical F-actin prevented activation of both SOC and TRP3 channels, which suggests that ER-PM interactions underlie coupling of both channels. A cell-permeant inhibitor of inositol trisphosphate receptor (InsP(2)R) function, 2-aminoethoxydiphenyl berate, prevented both receptor-induced TRP3 activation and receptor-induced SOC activation. It is concluded that InsP(3)Rs mediate both SOC and TRP channel opening and that the InsP(3)R is essential for maintaining coupling between store emptying and physiological activation of SOCs.