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

Ranvier节点离子通道聚集的分子机制研究。

• 批准号: 14580749
• 负责人: BABA Hiroko
• 金额: $ 1.98万
• 依托单位: Tokyo University of Pharmacy and Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580749/
• 关键词: voltage-gated sodium channel; voltage-gated potassium channel; the nodes of Ranvier; myelin; myelinated nerve fiber; sulfatide; oligodendrocyte; shcwann cell; サルファチド

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.

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。

项目成果

Ishibashi T, Ding L, Ikenaka K, Inoue Y, Miyado K, Mekada E, Baba H.: "Tetraspanin protein CD9 is a novel paranodal component regulating paranodal junctional formation."J Neurosci.. 24(1). 96-102 (2004)

Ishibashi T、Ding L、Ikenaka K、Inoue Y、Miyado K、Mekada E、Baba H.：“四跨膜蛋白 CD9 是调节节旁连接形成的新型节旁成分。”J Neurosci.. 24(1)。

Ishibashi, T., Ikenaka, K., Shimizu, T., Kagawa, T., Baba, H.: "Initiation of sodium channel clustering at the node of Ranvier in the mouse optic nerve."Neurochem.Res.. 28. 117-125 (2003)

Ishibashi, T.、Ikenaka, K.、Shimizu, T.、Kakawa, T.、Baba, H.：“钠通道在小鼠视神经 Ranvier 节点处聚集的起始。”Neurochem.Res.. 28。

Suzuki A, Hoshi T, Ishibashi T, Hayashi A, Yamaguchi Y, Baba H.: "Paranodal axoglial junction is required for the maintenance of the Nav1.6-type sodium channel in the node of Ranvier in the optic nerves but not in peripheral nerve fibers in the sulfatide-

Suzuki A、Hoshi T、Ishibashi T、Hayashi A、Yamaguchi Y、Baba H.：“视神经 Ranvier 结中的 Nav1.6 型钠通道的维持需要节点旁轴胶质连接，但在外周则不需要

Ishibashi T, Ikenaka K, Shimizu T, Kagawa T, Baba H.: "Initiation of sodium channel clustering at the node of Ranvier in the mouse optic nerve."Neurochem Res.. 28(1). 117-125 (2003)

Ishibashi T、Ikenaka K、Shimizu T、Kakawa T、Baba H.：“在小鼠视​​神经 Ranvier 节点处钠通道簇的启动。”Neurochem Res.. 28(1)。

Tomoko Ishibashi: "A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation"Journal of Neuroscience. 22・15. 6507-6514 (2002)

Tomoko Ishibashi：“髓磷脂半乳糖脂，硫苷脂，对于维持有髓轴突上的离子通道至关重要，但对于初始簇形成不是必需的”《神经科学杂志》22·15（2002）。