2000 Fiscal Year Annual Research Report

興奮性シナプスに発現するクラスタリング分子の神経薬理学的研究

Research Project

Project/Area Number	11470025
Research Institution	Kumamoto University
Principal Investigator	福永浩司熊本大学, 医学部, 助教授 (90136721)
Co-Investigator(Kenkyū-buntansha)	笠原二郎熊本大学, 医学部, 助手 (10295131) 山本秀幸熊本大学, 医学部, 講師 (60191433) 宮本英七熊本大学, 医学部, 教授 (50109659)
Keywords	シナプス可塑性 / クラスタリング分子 / NMDA受容体 / CaMキナーゼII / SAP102 / PSD-95 / PDZドメイン / long-term potentiation
Research Abstract	中枢神経系における興奮性シナプスでは受容体、細胞骨格蛋白質、シグナル伝達分子がクラスタリング分子あるいはscaffold(足場)蛋白質を介して結合して巨大な蛋白質複合体を形成している。本研究ではこれらの蛋白質複合体の形成が興奮性シナプス発達に伴って時間的、空間的にどのように制御されているのか。特に、シナプス活動依存性の制御機構について明らかにする。NMDA受容体のクラスタリング分子として、PSD-95/SAP90が知られているが、私達は新たにSAP102がNMDA受容体と結合することを明らかにした。培養海馬神経細胞ではNMDA受容体の発現に伴ってSAP102が発現し、免疫組織化学的検討ではシナプスにおいて共発現していた。CaMキナーゼIIはNMDA受容体と結合することが知られているが、SAP102をin vitro、in situでリン酸化することを明らかにした。さらに、海馬CAl領域の長期増強に伴ってSAP102がリン酸化されることを確認した。このリン酸化反応はCaMキナーゼIIによるものであり、CaMキナーゼIIの自己燐酸化反応と同様に、SAP102のリン酸化反応は持続的であった。in vitroの実験によってSAP102はリン酸化されると、NMDA受容体から解離することが解った。SAP102にはPSD-95との結合や一酸化窒素合成酵素などのシグナル伝達分子が結合している。海馬長期増強に伴うSAP102のリン酸化反応はNMDA受容体のクラスタリングとシグナル伝達分子のシナプスでの局在を変化させる可能性がある。さらに、リン酸化反応の機能的役割を追究する。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] K.Fukunaga: "Decreased protein phosphatase 2A activity in hippocampal long-term potentiation."J.Neurochem.. 74. 807-817 (2000)
[Publications] J.Kasahara: "Activation of Ca^<2+>/calmodulin-dependent protein kinase IV in cultured rat hippocampal neurons."J.Neurosci.Res.. 59. 594-600 (2000)
[Publications] K.Fukunaga: "Inhibition of neuronal nitric oxide synthase activity by 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel neuroprotective agent, in vitro and in cultured neuroblastoma cells in situ."Biochem.Pharmacol.. 60. 693-699 (2000)
[Publications] H.Kanasaki: "Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells."Biol.Reprod.. 62. 1486-1494 (2000)
[Publications] Y.Takeuchi: "Identification of the isoforms of Ca^<2+>/calmodulin-dependent protein kinase II in rat astrocytes and their subcellular localization."J.Neurochem.. 74. 2557-2567 (2000)
[Publications] H.Tabuchi: "Regulation of insulin secretion by overexpression of Ca^<2+>/calmodulin-dependent protein kinase II in insulinoma MIN6 cells."Endocrinology. 141. 2350-2360 (2000)
[Publications] I.Munir: "Expression of cyclo-oxygenase 2 by prostaglandin E2 in human endometrial adenocar-cinoma cell line HEC-1B."Biol.Reprod.. 63. 933-941 (2000)
[Publications] T.Moriya: "Close linkage between calcium/calmodulin kinase II α/βand NMDA-2A receptors in the lateral amygdala and significance for retrieval of auditory fear conditioning."Eur.J.Neurosci.. 12. 3307-3314 (2000)
[Publications] Q.Zhang: "Changes of free fetty acids and acyl-coas in rat brain hippocampal slice with tetraethy-lammonium-induced long-term potentiation."Biochem.Biophys.Res.Commun.. 267. 208-212 (2000)
[Publications] I.Munir: "Signaling pathways affecting cyclooxygenase 2 expression in endometrial epithelial cells."Recent Res.Devel.Endocrinol.. 1. 261-272 (2000)
[Publications] K.Fukunaga: "A working model of CaM kinase II activity in hippocampal long-term potentiation and memory."Neurosci.Res.. 38. 3-17 (2000)
[Publications] 福永浩司: "海馬における神経活動依存性シナプス伝達効率の調節."蛋白質核酸酵素,増刊「神経回路形成と機能発達」. 45. 474-482 (2000)
[Publications] S.-I.Yokota: "Involvement of calcium-calmodulin protein kinase but not of mitogen-activated protein kinase in light-induced phase delay and per gene expression in the suprachiasmatic nucleue of hamster."J.Neurochem.. (in press). (2001)
[Publications] T.Yonehara: "Involvement of mitogen-activated protein kinase in cAMP-induced hormone gene expression in rat pituitary GH3 cells."Endocrinology. (in press). (2001)
[Publications] E.Miyamoto: "Involvement of CaM kinase II and mitogen-activated protein kinase in hippocampal long-term potentiation. Neuroscientific Basis of Dementia (eds.: C.Tanaka,P.L.McGeer,Y.Ihara)"Birkhauser Verlag,Basel,Switzerland. 9 (2001)

2000 Fiscal Year Annual Research Report

興奮性シナプスに発現するクラスタリング分子の神経薬理学的研究

Principal Investigator

福永 浩司 熊本大学, 医学部, 助教授 (90136721)

Research Products

[Publications] K.Fukunaga: "Decreased protein phosphatase 2A activity in hippocampal long-term potentiation."J.Neurochem.. 74. 807-817 (2000)

[Publications] J.Kasahara: "Activation of Ca^<2+>/calmodulin-dependent protein kinase IV in cultured rat hippocampal neurons."J.Neurosci.Res.. 59. 594-600 (2000)

[Publications] H.Kanasaki: "Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells."Biol.Reprod.. 62. 1486-1494 (2000)

[Publications] Y.Takeuchi: "Identification of the isoforms of Ca^<2+>/calmodulin-dependent protein kinase II in rat astrocytes and their subcellular localization."J.Neurochem.. 74. 2557-2567 (2000)

[Publications] H.Tabuchi: "Regulation of insulin secretion by overexpression of Ca^<2+>/calmodulin-dependent protein kinase II in insulinoma MIN6 cells."Endocrinology. 141. 2350-2360 (2000)

[Publications] I.Munir: "Expression of cyclo-oxygenase 2 by prostaglandin E2 in human endometrial adenocar-cinoma cell line HEC-1B."Biol.Reprod.. 63. 933-941 (2000)

[Publications] T.Moriya: "Close linkage between calcium/calmodulin kinase II α/βand NMDA-2A receptors in the lateral amygdala and significance for retrieval of auditory fear conditioning."Eur.J.Neurosci.. 12. 3307-3314 (2000)

[Publications] Q.Zhang: "Changes of free fetty acids and acyl-coas in rat brain hippocampal slice with tetraethy-lammonium-induced long-term potentiation."Biochem.Biophys.Res.Commun.. 267. 208-212 (2000)

[Publications] I.Munir: "Signaling pathways affecting cyclooxygenase 2 expression in endometrial epithelial cells."Recent Res.Devel.Endocrinol.. 1. 261-272 (2000)

[Publications] K.Fukunaga: "A working model of CaM kinase II activity in hippocampal long-term potentiation and memory."Neurosci.Res.. 38. 3-17 (2000)

[Publications] 福永浩司: "海馬における神経活動依存性シナプス伝達効率の調節."蛋白質 核酸 酵素,増刊「神経回路形成と機能発達」. 45. 474-482 (2000)

[Publications] S.-I.Yokota: "Involvement of calcium-calmodulin protein kinase but not of mitogen-activated protein kinase in light-induced phase delay and per gene expression in the suprachiasmatic nucleue of hamster."J.Neurochem.. (in press). (2001)

[Publications] T.Yonehara: "Involvement of mitogen-activated protein kinase in cAMP-induced hormone gene expression in rat pituitary GH3 cells."Endocrinology. (in press). (2001)

[Publications] E.Miyamoto: "Involvement of CaM kinase II and mitogen-activated protein kinase in hippocampal long-term potentiation. Neuroscientific Basis of Dementia (eds.: C.Tanaka,P.L.McGeer,Y.Ihara)"Birkhauser Verlag,Basel,Switzerland. 9 (2001)

福永浩司熊本大学, 医学部, 助教授 (90136721)

[Publications] 福永浩司: "海馬における神経活動依存性シナプス伝達効率の調節."蛋白質核酸酵素,増刊「神経回路形成と機能発達」. 45. 474-482 (2000)