Ikeda Atsushi, Miyazaki Taisuke, Kakizawa Sho, Okuno Yasushi, Tsuchiya Soken, Myomoto Akira, Saito Shin-ya, Yamamoto Tetsuji, Yamazaki Tetsuo, Iino Masamitsu, Tsujimoto Gozoh, Watanabe Masahiko, Takeshima Hiroshi
Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Biochem Biophys Res Commun. 2007 Nov 23;363(3):835-9. doi: 10.1016/j.bbrc.2007.09.062. Epub 2007 Sep 24.
Junctional membrane complexes (JMCs) generated by junctophilins are required for Ca(2+)-mediated communication between cell-surface and intracellular channels in excitable cells. Knockout mice lacking neural junctophilins (JP-DKO) show severe motor defects and irregular cerebellar plasticity due to abolished channel crosstalk in Purkinje cells (PCs). To precisely understand aberrations in JP-DKO mice, we further analyzed the mutant PCs. During the induction of cerebellar plasticity via electrical stimuli, JP-DKO PCs showed insufficient depolarizing responses. Immunochemistry detected mild impairment in synaptic maturation and hyperphosphorylation of protein kinase Cgamma in JP-DKO PCs. Moreover, gene expression was slightly altered in the JP-DKO cerebellum. Therefore, the mutant PCs bear marginal but widespread abnormalities, all of which likely cause cerebellar motor defects in JP-DKO mice.
连接蛋白产生的连接膜复合物（JMCs）是可兴奋细胞中钙（Ca2+）介导的细胞表面与细胞内通道之间通讯所必需的。缺乏神经连接蛋白的敲除小鼠（JP-DKO）由于浦肯野细胞（PCs）中通道串扰被消除，表现出严重的运动缺陷和不规则的小脑可塑性。为了精确了解JP-DKO小鼠的异常情况，我们进一步分析了突变的PCs。在通过电刺激诱导小脑可塑性的过程中，JP-DKO PCs表现出不足的去极化反应。免疫化学检测到JP-DKO PCs中突触成熟存在轻度损伤以及蛋白激酶Cγ的过度磷酸化。此外，JP-DKO小鼠小脑中的基因表达略有改变。因此，突变的PCs存在轻微但广泛的异常，所有这些异常可能导致JP-DKO小鼠出现小脑运动缺陷。
