A T-type channel-calmodulin complex triggers αCaMKII activation.

A T-type channel-calmodulin complex triggers αCaMKII activation.
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DOI:
10.1186/s13041-017-0317-8
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发表时间:
2017-08-11
期刊:
影响因子:
3.6
通讯作者:
Turner RW
Turner RW
中科院分区:
医学3区
文献类型:
--
作者:
Asmara H;Micu I;Rizwan AP;Sahu G;Simms BA;Zhang FX;Engbers JDT;Stys PK;Zamponi GW;Turner RW

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钙调素(CaM)是一种重要的信号分子,通过激活参与细胞功能和可塑性的第二信使来调节大量的细胞功能。Cav 3家族的低电压激活的钙通道在介导低阈值钙内流中具有重要作用,但不被认为与CaM相互作用。我们发现钙调素和Cav3.1通道之间的组成性关联在休息,失去了通过活动依赖性和Cav3.1钙依赖性钙调素解离。此外,Cav 3钙内流足以激活细胞质中的α CaMK II,其方式取决于支持CaM相互作用所需的完整Cav3.1 C末端。因此,我们的研究结果表明,T型通道钙内流引起CaM和Cav3.1通道之间的一种新的动态相互作用,触发导致αCaMKII激活的信号级联反应。本文的在线版本(doi:10.1186/s13041-017-0317-8)包含补充材料,可供授权用户使用。
Calmodulin (CaM) is an important signaling molecule that regulates a vast array of cellular functions by activating second messengers involved in cell function and plasticity. Low voltage-activated calcium channels of the Cav3 family have the important role of mediating low threshold calcium influx, but were not believed to interact with CaM. We find a constitutive association between CaM and the Cav3.1 channel at rest that is lost through an activity-dependent and Cav3.1 calcium-dependent CaM dissociation. Moreover, Cav3 calcium influx is sufficient to activate αCaMKII in the cytoplasm in a manner that depends on an intact Cav3.1 C-terminus needed to support the CaM interaction. Our findings thus establish that T-type channel calcium influx invokes a novel dynamic interaction between CaM and Cav3.1 channels to trigger a signaling cascade that leads to αCaMKII activation. The online version of this article (doi:10.1186/s13041-017-0317-8) contains supplementary material, which is available to authorized users.
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