SEPT7-mediated regulation of Ca2+ entry through Orai channels requires other septin subunits
SEPT7-mediated regulation of Ca2+ entry through Orai channels requires other septin subunits
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DOI：
10.1002/cm.21476
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发表时间：
2019-01-01
期刊：
影响因子：
2.9
通讯作者：
Hasan, Gaiti
中科院分区：
文献类型：
--
作者：
Deb, Bipan K.;Hasan, Gaiti
Orai 通道是质膜驻留的 Ca2+ 通道，通过称为钙库操纵的 Ca2+ 进入 (SOCE) 的过程，在 ER-Ca2+ 库耗尽后允许细胞外 Ca2+ 摄取。 SEPT2 亚组的 Septin 在人类非兴奋性细胞中充当 SOCE 的正调节因子。 SEPT2亚组脓蛋白与SEPT6、SEPT7和SEPT9亚组脓蛋白形成异六聚体或异八聚体复合物的中心核心。较少的 septin 编码基因的存在加上易于遗传操作可以更好地了解果蝇中的 septin 亚组功能。我们早期的研究结果表明，虽然 dSEPT7 减少不会改变 SOCE 期间 Orai 介导的 Ca2+ 进入，但它会导致静息神经元中 Orai 通道的组成性激活。在这里，我们通过细胞和功能测定研究了其他 septin 亚组成员在调节果蝇神经元中 Orai 通道激活中的作用。我们发现，dSEPT1（SEPT2 亚组 septin）可以与 dSEPT2 和 dSEPT7 存在于果蝇中枢神经系统 (CNS) 的复合物中。我们的研究结果表明，减少不同亚组的脓蛋白后获得的脓蛋白丝和异聚体的性质改变了它们调节Orai通道开放的能力。脓毒症对 Orai 功能的这种复杂调节的分子机制需要进一步的细胞研究。
Orai channels are plasma membrane resident Ca2+ channels that allow extracellular Ca2+ uptake after depletion of ER-Ca2+ stores by a process called store-operated Ca2+ entry (SOCE). Septins of the SEPT2 subgroup act as positive regulators of SOCE in human nonexcitable cells. SEPT2 subgroup septins form the central core of hetero-hexameric or hetero-octameric complexes with SEPT6, SEPT7 and SEPT9 subgroup septins. The presence of fewer septin encoding genes coupled with ease of genetic manipulation allows for better understanding of septin subgroup function in Drosophila. Our earlier findings show that although dSEPT7 reduction does not alter Orai-mediated Ca2+ entry during SOCE, it results in constitutive activation of Orai channels in resting neurons. Here, we have investigated the role of other septin subgroup members in regulating Orai channel activation in Drosophila neurons by both cellular and functional assays. We show that dSEPT1, a SEPT2 subgroup septin can exist in a complex with dSEPT2 and dSEPT7 in the central nervous system (CNS) of Drosophila. Our findings suggest that the nature of septin filaments and heteromers obtained after reducing septins of different subgroups alters their ability to regulate Orai channel opening. The molecular mechanisms underlying this complex regulation of Orai function by septins require further cellular investigations.