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

我们研究了有髓鞘轴突中电压门控离子通道特征定位的分子机制：以下是本研究的结果。1)我们利用免疫沉淀分析了髓鞘蛋白CD9的蛋白复合体，该蛋白复合体促进了旁结（PJ）的形成。因此，CD9与整合素、claudini、MOG和CD81.2等膜蛋白形成复合物。我们使用sulfatide-deficient（CST KO）小鼠研究了PJ对钠通道亚型转换的影响。该突变体表现出PJ的破坏，改变了节点长度和通道分布。CNS突变体的结果表明，在发育过程中，PJ的形成对于节点Nav1.2完全替换为Nav1.6以及维持节点上的Nav1.6簇是必要的。3)在PNS中未观察到这种亚型异常，在PJ中观察到破坏。因此，PJ显著影响Nav1.6在节点中的保留，进而导致节点结构的紊乱。然而，它的重要性在中枢和周围神经系统之间可能有所不同。与CD9结合的分子可能对PJ的形成和节点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.