1998 Fiscal Year Final Research Report Summary
Molecular and cellular biological study about the abnormal neurite outgrowth and protein phosphorylation in temporal lobe epilepsy
| Project/Area Number |
09680766
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
YAMAMOTO Hideyuki Kumamoto University School of Medicine, Pharmacology, Assistant Professor, 医学部, 講師 (60191433)
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| Co-Investigator(Kenkyū-buntansha) |
KASAHARA Jiro Kumamoto University School of Medicine, Pharmacology, Instructor, 医学部, 助手 (10295131)
FUKUNAGA Kohji Kumamoto University School of Medicine, Pharmacology, Assoicate Professor, 医学部, 助教授 (90136721)
MIYAMOTO Eishichi Kumamoto University School of Medicine, Pharmacology, Professor, 医学部, 教授 (50109659)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Brain-derived neurotrophic factor (BDNF) / Ca^<2+> / calmodulin-dependent protein kinase II / Cytoskeletal proteins / Hippocampus / Naurite outgrowth / NG108-15 cells / Nuclear localization signal / Temporal lobe epilepsy |
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| Research Abstract |
A morphological characteristic of temporal lobe epilepsy consists of the abnormal neurite outgrowth of the hippocampal dentate granule cells. Some isoforms of Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) may be related to this abnormal neurite outgrowth. Among CaM kinase II, four subunits and several isoforms have been identified from brain. In order to investigate the pathophysiological roles of each isoform of CaM kinase II in temporal lobe epilepsy, we studied about the structures and functions of CaM kinase II isoforms mainly about the delta subunit of CaM kinase II (CaM kinase IIdelta). 1) We prepared the antibody against CaM kinase IIdelta and examined the localization of the subunit in brain. 2) We obtained the cDNAs of 6 isoforms of CaM kinase IIdelta from rat brain. Among these isoforms, delta3 was localized in the nuclei in transfected NG1O8-15 cells. 3) Overexpression of delta3 in NG1O8- 15 cells induced the gene expression of brain-derived neurotrophic factor (BDNF) which promotes survival and differentiation of specific populations of neurons in the brain. 4) We found that the major isoform of CaM kinase II in PC12 cells and NG108-15 cells was delta2. And delta2 appeared to be mainly localized in Golgi's apparatus.
5) Other isoforms were localized in the cytoplasm in NG 108-15 cells. Therefore, these isoforms may be involved in the regulation of neurite outgrowth via phosphorylation of cytoskeletal proteins such as microtubule-associated protein 2.
These results suggest that each isoform is localized in the specific site in neurons to play some important roles in neuronal functions.
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Research Products
(28 results)
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[Publications] Yamamoto, H.Matsumura, T., Kugiyama, K., Oishi, Y., Ogata, N., yasue, H.and Miyamoto, E.: "The antibody specific for myristoylated alanine-rich C Kinase substrate phosphorylated by protein kinase C : Activation of protein kinase C in smooth muscle cells in human coronary arteries." Arch.Biochem.Biophys.359. 151-159 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Takeuchi, Y., Yamamoto, H., Matsumoto, K., Kimura, T., Katsuragi, S., Miyakawa, T.and Miyamoto, E.: "Nuclear localization of the delta subunit of Ca^<2+>/calmodulin-dependent protein kinase II in rat cerebellar granule cells." J.Neurochem.72. 815-825 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsumoto, K., Ebihara, K., Yamamoto, H., Tabuchi, H., Fukunaga, K., Yasunami, M., Ohkubo, H., Shichiri, M and Miyamoto, E.: "Cloning from insulinoma cells of synapsin I associated with insulin secretory granules." J.Biol.Chem.274. 2053-2059 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakai, M., Hojo, K., Yagi, K., Saito, N., Taniguchi, T., Terashima, A., Kawamata, T., Hashimoto, T., Maeda, K., Gschwendt, M., Yamamoto, H., Miyamoto, E.and Tanaka, C.: "Amyloid beta protein (25-35) phosphorylates MARCKS through tyrosine kinase-activated protein kinase C signaling pathway in microglia." J.Neurochem.(in press). (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Miyamoto, E., Fukunaga, K., Yamamoto, H., Yano, S.and Muller, D.: Role of Ca^<2+>/calmodulin-dependent protein kinase II in neuronal regulation. In : Kinases and Phosphatases in Lymphocyte and Neuronal Signaling (ed. : H.Yakura). Springer-Verlag Tokyo, Tokyo, 252-261 (1997)
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「研究成果報告書概要(欧文)」より
