Store-independent modulation of Ca(2+) entry through Orai by Septin 7.
Store-independent modulation of Ca(2+) entry through Orai by Septin 7.
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DOI：
10.1038/ncomms11751
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发表时间：
2016-05-26
影响因子：
16.6
通讯作者：
Hasan G
中科院分区：
文献类型：
--
作者：
Deb BK;Pathak T;Hasan G
ORAI通道是多种细胞类型中存储操作的钙离子进入(SOCE)所必需的。Septins是一类GTP结合蛋白，在细胞内起扩散屏障的作用。在这里，我们展示了Septin 7在果蝇神经元中对Orai通道激活起‘分子刹车’的作用。降低Septin 7水平导致静息神经元中Dorai介导的钙离子内流和更高的细胞内钙离子。这种Ca~(2+)进入与内质网Ca~(2+)储备的耗竭和通过肌醇-1，4，5-三磷酸受体的Ca~(2+)释放无关。重要的是，通过ORAI的不依赖存储的钙离子进入弥补了果蝇飞行回路中SOCE的减少。此外，Septin 7的过表达减少了SOCE和飞行时间，支持了它在体内作为Orai通道功能的负调节因子的作用。因此，神经元中Septin 7的水平可以通过调节Orai功能和钙稳态来改变神经回路功能。众所周知，Orai通道可以调节商店操作的钙离子进入。在这里，作者表明，在果蝇飞行回路的神经元中，Septin 7作为Orai通道的负调节因子，令人惊讶的是，它通过Orai调节钙离子的储存非依赖性进入。
Orai channels are required for store-operated Ca2+ entry (SOCE) in multiple cell types. Septins are a class of GTP-binding proteins that function as diffusion barriers in cells. Here we show that Septin 7 acts as a ‘molecular brake’ on activation of Orai channels in Drosophila neurons. Lowering Septin 7 levels results in dOrai-mediated Ca2+ entry and higher cytosolic Ca2+ in resting neurons. This Ca2+ entry is independent of depletion of endoplasmic reticulum Ca2+ stores and Ca2+ release through the inositol-1,4,5-trisphosphate receptor. Importantly, store-independent Ca2+ entry through Orai compensates for reduced SOCE in the Drosophila flight circuit. Moreover, overexpression of Septin 7 reduces both SOCE and flight duration, supporting its role as a negative regulator of Orai channel function in vivo. Septin 7 levels in neurons can, therefore, alter neural circuit function by modulating Orai function and Ca2+ homeostasis. Orai channels are well known to mediate store-operated calcium entry. Here authors show that in neurons of the Drosophila flight circuit, Septin 7 acts as a negative regulator of Orai channels, surprisingly, by modulating store-independent calcium entry through Orai.