2003 Fiscal Year Final Research Report Summary
Molecular mechanisms of subcellular localization of the voltage-gated Ion channels
| Project/Area Number |
13480270
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Okazaki National Research Institutes |
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Principal Investigator |
IKENAKA Kazuhiro Okazaki National Research Institutes, National Institute for Physiological Sciences, Department of Molecular Physiology, Professor, 生理学研究所, 教授 (00144527)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHIRA Kensuke Saitama Medical School, Department of Physiology, Lecturer, 医学部, 講師 (10260043)
BABA Hiroko Tokyo University of Pharmacy and Life Science, Department of Molecular Neurobiology, Professor=, 薬学部, 教授 (40271499)
ONO Katsuhiko Okazaki National Research Institutes, National Institute for Physiological Sciences, Department of Molecular Physiology, Associate Professor, 生理学研究所, 助教授 (30152523)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Voltage-gated K channel / Voltage-gated Na channel / Synapse formation / node of Ranvier / paranodal junction / myelination / cerebellar granule neuron / paranodal junction |
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| Research Abstract |
Compartmentalization of neuronal function is achieved by highly localized clustering of ion channels in discrete subcellular membrane domains. Voltage-gated potassium (Ky) and sodium (Nay) channels exhibit highly variable cellular and subcellular patterns of expression. To understand how they are regulated, we focused on the two distinct subcellular domains: localization at synapses/dendrites and nodes of Ranvier.
Kv4.2, a voltage-gated K channel, shows somatodendritic localization in cerebellar granule cells. We found that its subcellular localization changes from soma to the dendrites and synapses during synaptogenesis, and the neuronal activity plays a key role in this change. This induction of localization was mediated by either NMDA or AMPA receptors.
Nav and Kv in myelinated axons show striking segregation at nodes of Ranvier. The axoglial paranodal junction is essential for the proper localization of these ion channels. We showed that sulfatide, a myeline glycolipid, and CD9,a member of the tetraspanin family, play an important role on the regulation of ion-channel localization through the formation of paranodal junction.
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[Publications] 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. 96-102 (2004)
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[Publications] Shibasaki, K., Nakahira, K., Trimmer, J., Shibata, R., Akita, M., Watanabe, S., Ikenaka, K.: "Mossy fiber contact triggers the targeting of Kv4.2 potassium channels to dendrites and synapses in developing cerebellar granule neurons"Journal of Neurochemistry. (in press).
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[Publications] Ishibashi, T., Dupree, J.L., Ikenaka, K., Hirahara,.Y., Honke, K., Peles, E., Popko, B., Suzuki, K., Nishino, H., Baba, H.: "A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation."J.Neurosci.. 22. 6507-6514 (2002)
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[Publications] Kawano, Y., Sasaki, M., Nakahira, K., Yoshimine, T., Shimizu, K., Wada, H., Ikenaka, K.: "Structural characterization and chromosomal localization of the MAGE-E1 gene."Gene. 277. 129-137 (2001)
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[Publications] Yamada, M., Jung, M., Kagawa, K., Ivanova, A., Nave, K.-A., Ikenaka, K.: "Mutant PLP/DM20 cannot be processed to secrete PLP-related oligodendrocyte differentiation/survival factor."Neurochem.Res.. 26. 639-645 (2001)
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[Publications] Sasaki, M., Nakahira, K., Kawano, Y., Katakura, H., Yoshimine, Y., Shimizu, K., Kim, S.U., Ikenaka, K.: "MAGE-E1, a new member of Melanoma-associated antigen gene family and its expression in human glioma."Cancer Res.. 61. 4809-4814 (2001)
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[Publications] Espinosa de los Monteros, A., Baba, H., Zhao, M., Pan, T., Chang, R., de Vellis, J., Ikenaka, K.: "Remyelination of the adult demyelinated mouse brain by grafted oligodendrocyte progenitors."Neurochem.Res.. 26. 673-682 (2001)
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