Studies on molecular mechanisms of ion channel clustering at the nodes of Ranvier.

我们对有髓轴突电压门控离子通道定位的分子机制进行了研究：1)用免疫沉淀法分析了髓鞘蛋白CD9与结旁连接(PJ)形成的蛋白质复合体，结果CD9与整合素、Claudini、Mog和CD81.2)我们用硫脂缺失(CST KO)小鼠检测了PJ对钠通道亚型转换的影响。突变体表现出PJ的中断，改变了节点的长度和通道分布。突变体CNS的结果表明，PJ的形成对于在发育过程中完全取代Nav1.2到Nav1.6以及节点上的Nav1.6簇的维持是必要的。3)这种亚型的异常在PNS中没有出现，那里观察到PJ中断。因此，PJ显著地影响了Nav1.6在节点中的保持，随后是节点结构的破坏CD9在中枢神经系统和外周神经系统中的重要性可能不同。CD9结合的分子可能对结节内PJ的形成和离子通道的维持有一定的作用。

We have studied the molecular mechanisms of characteristic localizations of voltage-gated ion channels in myelinated axons : The followings are the results in the present study.1) We analyzed protein complex with myelin protein CD9, which contributed to the formation of paranodal junction(PJ)using immunoprecipitation.As a result, CD9 formed a complex with membrane proteins such as integrin, claudini, MOG as well as CD81.2)We examined the influence of PJ on switching of sodium channel subtypes using the sulfatide-deficient(CST KO)mouse.This mutant displayed disruption of PJ and altered nodal lengths and channel distributions.The results in the mutant CNS suggested that PJ formation is necessary for complete replacement of nodal Nav1.2 to Nav1.6 during development as well as maintenance of Nav1.6 clusters at the nodes.3) Such subtype abnormality was not cbserved in the PNS, where PJ disruption was observed.Thus, PJ significantly influences the retention of Nav1.6 in the node, which is followed by disorganization of nodal structures.However, its importance may differ between the central and peripheral nervous system.The molecules those bind to CD9 may have some roles for the formation of PJ and maintenance of ion channels in the nodes.