Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.
Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell Rep. 2017 Aug 22;20(8):1855-1866. doi: 10.1016/j.celrep.2017.07.074.
The homeostatic control of presynaptic neurotransmitter release stabilizes information transfer at synaptic connections in the nervous system of organisms ranging from insect to human. Presynaptic homeostatic signaling centers upon the regulated membrane insertion of an amiloride-sensitive degenerin/epithelial sodium (Deg/ENaC) channel. Elucidating the subunit composition of this channel is an essential step toward defining the underlying mechanisms of presynaptic homeostatic plasticity (PHP). Here, we demonstrate that the ppk1 gene encodes an essential subunit of this Deg/ENaC channel, functioning in motoneurons for the rapid induction and maintenance of PHP. We provide genetic and biochemical evidence that PPK1 functions together with PPK11 and PPK16 as a presynaptic, hetero-trimeric Deg/ENaC channel. Finally, we highlight tight control of Deg/ENaC channel expression and activity, showing increased PPK1 protein expression during PHP and evidence for signaling mechanisms that fine tune the level of Deg/ENaC activity during PHP.
内稳态控制的突触前神经递质释放稳定的信息传递在神经系统的生物从昆虫到人类。突触前内稳态信号中心在于调节膜插入阿米洛利敏感的退化/上皮钠通道（ Deg / ENaC ）。阐明该通道的亚基组成是定义突触前内稳态可塑性（ PHP ）的潜在机制的重要步骤。在这里，我们证明了 ppk1 基因编码这个 Deg / ENaC 通道的一个必需亚基，在运动神经元中起作用，以快速诱导和维持 PHP 。我们提供了遗传和生化证据表明， PPK1 与 PPK11 和 PPK16 一起作为一个突触前的，异三聚体 Deg / ENaC 通道。最后，我们强调 Deg / ENaC 通道表达和活性的严格控制，在 PHP 期间显示出 PPK1 蛋白表达增加，并证明了信号机制可以精细调节 PHP 期间 Deg / ENaC 活性的水平。
