2001 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)	竹内有輔熊本大学, 医学部, 助手 (90336214) 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	NMDA受容体 / scafold protein / CaMキナーゼII / PSD-95 / SAP102 / ドーパミン受容体 / 海馬 / シナプス
Research Abstract	齧歯類の中枢神経系の興奮性シナプスではNMDA受容体の構成サブユニットが発達に伴ってNMDAR2BからNMDAR2Aに変化することが知られている。同時にNMDA受容体の主要なクラスタリング分子はNE-dlg/SAP102からPSD-95に変化していく。福永、宮本らはNE-dlgとNMDAR2B受容体との結合様式をラット脳シナプトソームを用いて検討した。カルシウム/カルモデュリンはNE-dlgとNMDAR2B受容体結合を強化するが、CaMキナーゼIIによるリン酸化反応によってNE-dlg/SAP102はNMDAR2Bから解離した。培養海馬神経細胞をグルタミン酸で刺激した後に活性型CaMキナーゼII, NMDAR2B、NMDAR2A、NE-dlg/SAP102、PSD-95の細胞内局在について検討した。NMDA受容体阻害剤とCaMキナーゼII阻害剤で培養細胞を処理すると、NMDAR2B、NE-dlgとPSD-95の膜での発現が有意に阻害された。NMDA2Aの発現には影響しない。以上のことからCaMキナーゼIIは細胞膜におけるNMDAR2Bの発現とNMDA受容体のクラスタリングに関与することが明らかとなった。竹内らは細胞分子生物学的手法を用いてCaMキナーゼIIがドーパミン受容体のゴルジ装置から細胞膜へのトランスポートに関与するという新しい知見を得た。CaMキナーゼIIの膜への輸送にはドーパミン受容体のC末端のシークエンスが重要であること、そのC末端に結合する分子を同定した。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] T.Yonehara: "Involvement of mitogen-activated protein kinase in cyclic adenosine 3', 5'-monophosphate-induced hormone gene expression in rat pituitary GH_3 cells"Endocrinology. 142. 2811-2819 (2001)
[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 nucleus of hamster"J. Neurochem.. 77. 618-627 (2001)
[Publications] S.Yano: "Activation of Akt/Protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus"J. Cereb. Blood Flow Metab.. 21. 351-360 (2001)
[Publications] J.Kasahara: "Activation of calcium/calmodulin-dependent protein kinase IV in long term potentiation in the rat hippocampal CA1 region"J. Biol. Chem.. 276. 24044-24050 (2001)
[Publications] M.Nakai: "Amyloid β protein activates PKC-δ and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia"Neurochem. Int.. 38. 593-600 (2001)
[Publications] H.Hasegawa: "Microglial signaling by amyloid β protein through mitogen-activated protein kinase mediating phosphorylation of MARCKS"Neuroreport. 12. 2567-2571 (2001)
[Publications] T.Kawano: "Neuroprotective effect of sodium orthovanadate on delayed neuronal death after transient forebrain ischemia in gerbil hippocampus"J. Cereb. Blood Flow Metab.. 21. 1268-1280 (2001)
[Publications] M.Morioka: "Intravenously injected FK506 failed to inhibit hippocampal calcineurin"Biochem. Biophys. Res. Commun.. 286. 802-806 (2001)
[Publications] H.Kanasaki: "Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone. A role of mitogen-activated protein kinase signaling cascade in rat pituitary GH3 cells"Biol. Reprod.. (in press). (2002)
[Publications] E.Miyamoto: "Invovement of CaM kinase II and mitogen-activated protein kinase in hippocampal long-term potentiation. In : Neuroscientific Bases of Dementia(eds. : C.Tanaka, P.L.McGeer, Y.Ihara)"Birkhauser Verlag, Basel, Switzerland. 9 (2001)
[Publications] K.Fukunaga: "Differential role of CaM kinase II and IV activities in neuronal plasticity and memory. In : Recent Research Developments in Neurochemistry"Research Signpost, Trivandrum, India (in press). (2002)

2001 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] T.Yonehara: "Involvement of mitogen-activated protein kinase in cyclic adenosine 3', 5'-monophosphate-induced hormone gene expression in rat pituitary GH_3 cells"Endocrinology. 142. 2811-2819 (2001)

[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 nucleus of hamster"J. Neurochem.. 77. 618-627 (2001)

[Publications] S.Yano: "Activation of Akt/Protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus"J. Cereb. Blood Flow Metab.. 21. 351-360 (2001)

[Publications] J.Kasahara: "Activation of calcium/calmodulin-dependent protein kinase IV in long term potentiation in the rat hippocampal CA1 region"J. Biol. Chem.. 276. 24044-24050 (2001)

[Publications] M.Nakai: "Amyloid β protein activates PKC-δ and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia"Neurochem. Int.. 38. 593-600 (2001)

[Publications] H.Hasegawa: "Microglial signaling by amyloid β protein through mitogen-activated protein kinase mediating phosphorylation of MARCKS"Neuroreport. 12. 2567-2571 (2001)

[Publications] T.Kawano: "Neuroprotective effect of sodium orthovanadate on delayed neuronal death after transient forebrain ischemia in gerbil hippocampus"J. Cereb. Blood Flow Metab.. 21. 1268-1280 (2001)

[Publications] M.Morioka: "Intravenously injected FK506 failed to inhibit hippocampal calcineurin"Biochem. Biophys. Res. Commun.. 286. 802-806 (2001)

[Publications] H.Kanasaki: "Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone. A role of mitogen-activated protein kinase signaling cascade in rat pituitary GH3 cells"Biol. Reprod.. (in press). (2002)

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

[Publications] K.Fukunaga: "Differential role of CaM kinase II and IV activities in neuronal plasticity and memory. In : Recent Research Developments in Neurochemistry"Research Signpost, Trivandrum, India (in press). (2002)

福永浩司熊本大学, 医学部, 助教授 (90136721)