Stac protein regulates release of neuropeptides

Stac protein regulates release of neuropeptides
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DOI:
10.1073/pnas.2009224117
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发表时间:
2020-11-24
影响因子:
11.1
通讯作者:
Kuwada, John Y.
Kuwada, John Y.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hsu, I-Uen;Linsley, Jeremy W.;Kuwada, John Y.

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神经肽对于调节许多神经功能和行为很重要。神经肽的释放需要持久、高水平的胞质 Ca2+。然而,神经肽释放的分子调节仍有待阐明。最近,Stac3 被确定为脊椎动物骨骼肌中 L 型 Ca2+ 通道 (CaChs) 和兴奋-收缩耦合的关键调节因子。脊椎动物中有一个 stac 基因小家族,其他成员由中枢神经系统中的神经元亚群表达。然而,人们对神经 Stac 蛋白的功能知之甚少。果蝇含有一个 stac 基因 Dstac,该基因由肌肉和一部分神经元(包括表达神经肽的运动神经元)表达。在这里,基因操作,加上免疫标记、Ca2+成像、电生理学和行为分析,揭示了 Dstac 调节果蝇运动神经元中的 L 型 CaChs (Dmca1D),而这反过来又控制神经肽的释放。
Neuropeptides are important for regulating numerous neural functions and behaviors. Release of neuropeptides requires long-lasting, high levels of cytosolic Ca2+. However, the molecular regulation of neuropeptide release remains to be clarified. Recently, Stac3 was identified as a key regulator of L-type Ca2+ channels (CaChs) and excitation-contraction coupling in vertebrate skeletal muscles. There is a small family of stac genes in vertebrates with other members expressed by subsets of neurons in the central nervous system. The function of neural Stac proteins, however, is poorly understood. Drosophila melanogaster contain a single stac gene, Dstac, which is expressed by muscles and a subset of neurons, including neuropeptide-expressing motor neurons. Here, genetic manipulations, coupled with immunolabeling, Ca2+ imaging, electrophysiology, and behavioral analysis, revealed that Dstac regulates L-type CaChs (Dmca1D) in Drosophila motor neurons and this, in turn, controls the release of neuropeptides.