钙调蛋白通过与瞬时受体电位通道蛋白1（TrpC1）C末端的一个位点相互作用，调节钙库操纵的钙离子内流的钙依赖性反馈抑制。
Calmodulin regulates Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) influx by interaction with a site in the C terminus of TrpC1.
作者信息
Singh Brij B, Liu Xibao, Tang Jisen, Zhu Michael X, Ambudkar Indu S
机构信息
Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Mol Cell. 2002 Apr;9(4):739-50. doi: 10.1016/s1097-2765(02)00506-3.
The mechanism involved in Ca(2+)-dependent feedback inhibition of store-operated Ca(2+) entry (SOCE) is not yet known. Expression of Ca(2+)-insensitive calmodulin (Mut-CaM) but not wild-type CaM increased SOCE and decreased its Ca(2+)-dependent inactivation. Expression of TrpC1 lacking C terminus aa 664-793 (TrpC1DeltaC) also attenuated Ca(2+)-dependent inactivation of SOCE. CaM interacted with endogenous and expressed TrpC1 and with GST-TrpC1 C terminus but not with TrpC1DeltaC. Two CaM binding domains, aa 715-749 and aa 758-793, were identified. Expression of TrpC1Delta758-793 but not TrpC1Delta715-749 mimicked the effects of TrpC1DeltaC and Mut-CaM on SOCE. These data demonstrate that CaM mediates Ca(2+)-dependent feedback inhibition of SOCE via binding to a domain in the C terminus of TrpC1. These findings reveal an integral role for TrpC1 in the regulation of SOCE.
钙库操纵性钙内流（SOCE）的钙离子（Ca2+）依赖性反馈抑制所涉及的机制尚不清楚。表达对Ca2+不敏感的钙调蛋白（Mut-CaM）而非野生型钙调蛋白会增加SOCE并减少其Ca2+依赖性失活。缺失C末端第664 - 793位氨基酸的瞬时受体电位通道蛋白1（TrpC1DeltaC）的表达也减弱了SOCE的Ca2+依赖性失活。钙调蛋白与内源性及表达的TrpC1以及谷胱甘肽-S-转移酶-TrpC1 C末端相互作用，但不与TrpC1DeltaC相互作用。鉴定出两个钙调蛋白结合结构域，即第715 - 749位氨基酸和第758 - 793位氨基酸。表达TrpC1Delta758 - 793而非TrpC1Delta715 - 749模拟了TrpC1DeltaC和Mut-CaM对SOCE的影响。这些数据表明，钙调蛋白通过与TrpC1 C末端的一个结构域结合来介导SOCE的Ca2+依赖性反馈抑制。这些发现揭示了TrpC1在SOCE调节中的重要作用。
Zotero 插件