Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.
Cell and Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109.
Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29914-29924. doi: 10.1073/pnas.2009224117. Epub 2020 Nov 9.
Neuropeptides are important for regulating numerous neural functions and behaviors. Release of neuropeptides requires long-lasting, high levels of cytosolic Ca However, the molecular regulation of neuropeptide release remains to be clarified. Recently, Stac3 was identified as a key regulator of L-type Ca channels (CaChs) and excitation-contraction coupling in vertebrate skeletal muscles. There is a small family of 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. contain a single gene, , which is expressed by muscles and a subset of neurons, including neuropeptide-expressing motor neurons. Here, genetic manipulations, coupled with immunolabeling, Ca imaging, electrophysiology, and behavioral analysis, revealed that Dstac regulates L-type CaChs (Dmca1D) in motor neurons and this, in turn, controls the release of neuropeptides.
神经肽对于调节多种神经功能和行为至关重要。神经肽的释放需要持续的、高水平的细胞质 Ca2+。然而，神经肽释放的分子调节仍有待阐明。最近，Stac3 被鉴定为脊椎动物骨骼肌中 L 型 Ca 通道（CaChs）和兴奋-收缩偶联的关键调节剂。脊椎动物中有一小家族基因，其他成员由中枢神经系统中神经元的亚群表达。然而，神经 Stac 蛋白的功能知之甚少。Dstac 含有一个单一的基因，它在肌肉和包括表达神经肽的运动神经元在内的神经元的亚群中表达。在这里，遗传操作，结合免疫标记、Ca 成像、电生理学和行为分析，揭示了 Dstac 在运动神经元中调节 L 型 CaChs（Dmca1D），这反过来又控制神经肽的释放。
