小柯机器人

美国国立卫生研究院Wei Lu团队发现，Shisa7是一种GABAA受体辅助亚基（GABAARs），控制苯二氮卓类药物的功能。该项研究成果发表在2019年10月11日出版的《科学》杂志上。

他们发现Shisa7是一种单程跨膜蛋白，位于GABA能抑制突触并与GABAARs相互作用。 Shisa7控制突触中的受体丰度并加快通道失活动力学。Shisa7还可以有效地增强diazepam（地西泮，一种经典的苯二氮卓类药物）对GABAAR的作用。Shisa7的基因缺失选择性地损害GABA能传递，并降低了diazepam对小鼠的影响。

他们的数据表明，Shisa7调节GABAAR的运输、功能和药理作用，并揭示了调节脑中苯二氮卓作用的先前未知的分子相互作用。

研究人员表示，GABAARs的功能和药理学具有重要的生理和临床意义，长期以来一直被认为是由通道孔形成亚基决定的。

附：英文原文

Title: Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions

Author: Wenyan Han, Jun Li, Kenneth A. Pelkey, Saurabh Pandey, Xiumin Chen, Ya-Xian Wang, Kunwei Wu, Lihao Ge, Tianming Li, David Castellano, Chengyu Liu, Ling-Gang Wu, Ronald S. Petralia, Joseph W. Lynch, Chris J. McBain, Wei Lu

Issue&Volume: Volume 366 Issue 6462

Abstract: 

The function and pharmacology of γ-aminobutyric acid type A receptors (GABAARs) are of great physiological and clinical importance and have long been thought to be determined by the channel pore–forming subunits. We discovered that Shisa7, a single-passing transmembrane protein, localizes at GABAergic inhibitory synapses and interacts with GABAARs. Shisa7 controls receptor abundance at synapses and speeds up the channel deactivation kinetics. Shisa7 also potently enhances the action of diazepam, a classic benzodiazepine, on GABAARs. Genetic deletion of Shisa7 selectively impairs GABAergic transmission and diminishes the effects of diazepam in mice. Our data indicate that Shisa7 regulates GABAAR trafficking, function, and pharmacology and reveal a previously unknown molecular interaction that modulates benzodiazepine action in the brain.

DOI: 10.1126/science.aax5719

Source:https://science.sciencemag.org/content/366/6462/246