1999 Fiscal Year Annual Research Report

海馬シナプス可塑性におけるカルモデュリンキナーゼIIの役割

Research Project

Project/Area Number	11170244
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	long-term potentiation / CaMキナーゼII / NMDA受容体 / AMPA受容体 / シナプス可塑性 / クラスタリング分子 / SAP102 / PSD-95
Research Abstract	海馬Ca1領域でのシナプス伝達長期増強(LTP)は学習・記憶の素過程である。カルモデュリン(CaM)キナーゼIIの自己燐酸化反応はLTPの発現に直接関与している。学習・記憶に伴って,シナプスではNMDA受容体のみが発現するサイレントシナプスから,AMPA受容体を有する機能性シナプスへの変換が起こる。本研究ではシナプスにおけるCaMキナーゼIIの標的分子を明らかにして,機能性シナプス発現の分子素過程を追及した。CaMキナーゼIIの自己燐酸化反応を特異的に認識する抗体を用いて,CA1におけるLTP発現後のCaMキナーゼIIの活性化部位を免疫組織化学的手法で解析した。活性型CaMキナーゼIIの免疫染色性の上昇はCA1錐体細胞の樹上突起,スパインで顕著であり,細胞体においても観察された。さらに,活性型CaMキナーゼIIが上昇している細胞では,細胞体と樹上突起においてAMPA受容体(GluR-2)の蓄積が見られた。今後は,スパインにおけるCaMキナーゼIIの活性化反応と燐酸化型AMPA受容体の発現について共焦点レーザー顕微鏡にて解析する予定である。AMPA受容体と同様に,NMDA受容体のスパインでの発現はシナプス活動によって調節される。PDZドメインを有するNMDA受容体のクラスタリング分子,SAP102(NE-dlg)がカルシウム/カルモデュリンおよびPSD-95と結合すること,CaMキナーゼIIによって燐酸化されることを見出した。サイレントシナプスから機能性シナプスへの変換におけるカルモデュリン,CaMキナーゼIIの作用機構をさらに解析する予定である。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] M. Ohmitsu: "Phosphorylation of myristoylated alanine-rich protein kinase C substrate by mitogen-activated protein kinase in cultured rat hippocampal neurons following stimulation of glutamate receptors."J. Biol. Chem.. 274. 408-417 (1999)
[Publications] K. Matsumoto: "Cloning from insulinoma cells of synapsin I associated with insulin secretory granules."J. Biol. Chem.. 274. 2053-2059 (1999)
[Publications] N. Masuko: "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90: A possible regulatory role in molecular clustering at synaptic sites."J. Biol. Chem.. 274. 5782-5790 (1999)
[Publications] J. Kasahara: "Differential effects of a calcineurin inhibitor on glutamate-induced phosphorylation of Ca^<2+>/calmodulin-dependent protein kinase in cultured rat hippocampal neurons."J. Biol. Chem.. 274. 9061-9067 (1999)
[Publications] H. Kuwahara: "A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP102 and N-Methyl-D-aspartate receptor."J. Biol. Chem.. 274. 32204-32214 (1999)
[Publications] J. Liu: "Differential roles of Ca^<2+>/calmodulin-dependent protein kinase II and mitogen-activated protein kinase activation in hippocampal long-term potentiation."J. Neurosci.. 19. 8292-8299 (1999)
[Publications] M. Morioka: "Activities of calcineurin and phosphatase 2A in the hippocampus after transient forebrain ischemia."Brain Res.. 828. 135-144 (1999)
[Publications] H. Kanasaki: "Mitogen-activated protein kinase activation by stimulation with thyrotropin-releasing hormone in rat pituitary GH3 cells."Biol. of Reprod.. 61. 319-325 (1999)
[Publications] I. Munir: "Mitogen-activated protein kinase activation and regulation of cyclooxygenase 2 expression by platelet-activating factor and hCG in human endometrial adenocarcinoma cell line HEC-1B."J. Reprod. Fertil.. 117. 49-59 (1999)
[Publications] Q. Zhang: "Changes of free fatty acids and acyl-coas in rat brain hippocampal slice with tetraethylammonium-induced long-term potentiation."Biochem. Biophys. Res. Commun.. 267. 208-212 (1999)
[Publications] K. Fukunaga: "Current studies on a working model of CaM kinase II in hippocampal long-term potentiation and memory."Jpn. J. Pharmacol.. 79. 7-15 (1999)
[Publications] 福永浩司: "海馬における神経活動依存性シナプスの伝達効率の調節"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] 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: "Decreased protein phosphatase 2A activity in hippocampal long-term potentiation."J. Neurochem.. (in press). (2000)
[Publications] K. Fukunaga: "Inhibition of neuronal nitric oxide synthase activity by DY-9760e, a novel neuroprotective agent, in vitro and in cultured neuroblastoma cells in situ."Biochem. Pharmacol.. (in press). (2000)
[Publications] H. Kanasaki: "Involvement of p38 mitogen-activated protein kinase activation in bromocriptine-induced apoptosis in rat pituitary GH3 cells."Biol. of Reprod.. (in press). (2000)
[Publications] 宮本英七: "脳と神経:分子神経生物科学入門(編集:金子章道,川村光毅,植村慶一)第3章神経情報の統合,5.脳可塑性"共立出版. 7 (1999)

1999 Fiscal Year Annual Research Report

海馬シナプス可塑性におけるカルモデュリンキナーゼIIの役割

Principal Investigator

福永 浩司 熊本大学, 医学部, 助教授 (90136721)

Research Products

[Publications] M. Ohmitsu: "Phosphorylation of myristoylated alanine-rich protein kinase C substrate by mitogen-activated protein kinase in cultured rat hippocampal neurons following stimulation of glutamate receptors."J. Biol. Chem.. 274. 408-417 (1999)

[Publications] K. Matsumoto: "Cloning from insulinoma cells of synapsin I associated with insulin secretory granules."J. Biol. Chem.. 274. 2053-2059 (1999)

[Publications] N. Masuko: "Interaction of NE-dlg/SAP102, a neuronal and endocrine tissue-specific membrane-associated guanylate kinase protein, with calmodulin and PSD-95/SAP90: A possible regulatory role in molecular clustering at synaptic sites."J. Biol. Chem.. 274. 5782-5790 (1999)

[Publications] J. Kasahara: "Differential effects of a calcineurin inhibitor on glutamate-induced phosphorylation of Ca^<2+>/calmodulin-dependent protein kinase in cultured rat hippocampal neurons."J. Biol. Chem.. 274. 9061-9067 (1999)

[Publications] H. Kuwahara: "A novel NE-dlg/SAP102-associated protein, p51-nedasin, related to the amidohydrolase superfamily, interferes with the association between NE-dlg/SAP102 and N-Methyl-D-aspartate receptor."J. Biol. Chem.. 274. 32204-32214 (1999)

[Publications] J. Liu: "Differential roles of Ca^<2+>/calmodulin-dependent protein kinase II and mitogen-activated protein kinase activation in hippocampal long-term potentiation."J. Neurosci.. 19. 8292-8299 (1999)

[Publications] M. Morioka: "Activities of calcineurin and phosphatase 2A in the hippocampus after transient forebrain ischemia."Brain Res.. 828. 135-144 (1999)

[Publications] H. Kanasaki: "Mitogen-activated protein kinase activation by stimulation with thyrotropin-releasing hormone in rat pituitary GH3 cells."Biol. of Reprod.. 61. 319-325 (1999)

[Publications] I. Munir: "Mitogen-activated protein kinase activation and regulation of cyclooxygenase 2 expression by platelet-activating factor and hCG in human endometrial adenocarcinoma cell line HEC-1B."J. Reprod. Fertil.. 117. 49-59 (1999)

[Publications] Q. Zhang: "Changes of free fatty acids and acyl-coas in rat brain hippocampal slice with tetraethylammonium-induced long-term potentiation."Biochem. Biophys. Res. Commun.. 267. 208-212 (1999)

[Publications] K. Fukunaga: "Current studies on a working model of CaM kinase II in hippocampal long-term potentiation and memory."Jpn. J. Pharmacol.. 79. 7-15 (1999)

[Publications] 福永浩司: "海馬における神経活動依存性シナプスの伝達効率の調節"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] 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: "Decreased protein phosphatase 2A activity in hippocampal long-term potentiation."J. Neurochem.. (in press). (2000)

[Publications] K. Fukunaga: "Inhibition of neuronal nitric oxide synthase activity by DY-9760e, a novel neuroprotective agent, in vitro and in cultured neuroblastoma cells in situ."Biochem. Pharmacol.. (in press). (2000)

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

[Publications] 宮本英七: "脳と神経:分子神経生物科学入門(編集:金子章道,川村光毅,植村慶一)第3章 神経情報の統合,5.脳可塑性"共立出版. 7 (1999)

福永浩司熊本大学, 医学部, 助教授 (90136721)

[Publications] 宮本英七: "脳と神経:分子神経生物科学入門(編集:金子章道,川村光毅,植村慶一)第3章神経情報の統合,5.脳可塑性"共立出版. 7 (1999)