Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan.
Sci Rep. 2017 Apr 3;7:45646. doi: 10.1038/srep45646.
Vilse/Arhgap39 is a Rho GTPase activating protein (RhoGAP) and utilizes its WW domain to regulate Rac/Cdc42-dependent morphogenesis in Drosophila and murine hippocampal neurons. However, the function of Vilse in mammalian dendrite architecture and synaptic plasticity remained unclear. In the present study, we aimed to explore the possible role of Vilse in dendritic structure and synaptic function in the brain. Homozygous knockout of Vilse resulted in premature embryonic lethality in mice. Changes in dendritic complexity and spine density were noticed in hippocampal neurons of Camk2a-Cre mediated forebrain-specific Vilse knockout (Vilse) mice. Vilse mice displayed impaired spatial memory in water maze and Y-maze tests. Electrical stimulation in hippocampal CA1 region revealed that the synaptic transmission and plasticity were defected in Vilse mice. Collectively, our results demonstrate that Vilse is essential for embryonic development and required for spatial memory.
Vilse/Arhgap39 是一种 Rho GTP 酶激活蛋白(RhoGAP),它利用其 WW 结构域来调节果蝇和鼠海马神经元中 Rac/Cdc42 依赖性形态发生。然而,Vilse 在哺乳动物树突结构和突触可塑性中的功能尚不清楚。在本研究中,我们旨在探索 Vilse 在大脑中树突结构和突触功能中的可能作用。Vilse 基因的纯合敲除导致小鼠胚胎致死。在 Camk2a-Cre 介导的大脑前部特异性 Vilse 敲除(Vilse)小鼠的海马神经元中,发现树突复杂性和棘密度发生变化。Vilse 小鼠在水迷宫和 Y 迷宫测试中表现出空间记忆受损。在海马 CA1 区进行电刺激显示,Vilse 小鼠的突触传递和可塑性存在缺陷。总之,我们的结果表明,Vilse 对于胚胎发育是必需的,并且对于空间记忆是必需的。