2001 Fiscal Year Annual Research Report

神経可塑性と脳の発生・分化におけるIP_3受容体/Ca^<2+>シグナリングの役割

Research Project

Project/Area Number	13308044
Research Institution	The University of Tokyo
Principal Investigator	御子柴克彦東京大学, 医科学研究所, 教授 (30051840)
Keywords	IP_3レセプター / カルシウムシグナリング / 神経可塑性 / 脳の発生・分化 / シナプス / 長期増強 / 長期抑圧 / IP_3レセプター欠損マウス
Research Abstract	神経活動に依存したシナプスの調節は、神経系の発達と可塑性に不可欠である。シナプス前ニューロンと後ニューロンが繰り返し協調的に活性化されると、シナプス伝達効率は持続的に増強もしくは抑圧される。この現象をそれぞれ長期増強(LTP)長期抑圧(LTD)という。LTP、LTDに関して未解明の重要問題は、それらがどの程度当該シナプスに限定されて起こるのかという点である。今回、海馬CA1領域でNMDA(N-メチル-D-アスパラギン酸)受容体を部分的に抑制してCa流入を減らすと、LTPがLTDに変わり、LTPの入力特異性が消失して入力シナプス以外のシナプスでの(異シナプス性の)LTDが出現することを見いだした。同シナプス性LTDの誘導には、イノシトール三リン酸(InsP_3)受容体が必要である。1型のInsP_3受容体を薬理学的に阻害したり、遺伝的に欠損させると、LTDは消失する。したがって、シナプス後部位でのCa^<2+>濃度上昇のうち、細胞外からのCa^<2+>流入に加えて、リアノジン受容体あるいはInsP_3受容体を介するカルシウムの放出がそれぞれ活動依存性にシナプス調節作用の方向性と入力特異性を決定するものと考えられる。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Iwasaki, H. et al.: "2-Aminoethoxydiphenyl Borate (2-APB) Inhibits Capacitative Calcium Entry Independently of the Function of Inositol 1, 4, 5-Trisphosphate Receptors"Receptors & Channels. 7. 429-439 (2001)
[Publications] Fukuda, M. et al.: "Formation of Crystalloid Endoplasmic Recticulum Induced by Expression of Synaptotagmin Lacking the Conserved WHXL Motif in the C Terminus"J. Biol. Chem.. 276. 41112-41119 (2001)
[Publications] Fukuda, M. et al.: "Mechanism of the SDS-resistant Synaptotagmin Clustering Mediated by the Cysteine Cluster at the Interface between the Transmembrane and spacer Domains"J. Biol. Chem.. 276. 40319-40325 (2001)
[Publications] Fukuda, M. et al.: "Mechanism of the calcium-dependent multimerization of synaptotagmin VII mediated by its first and second C2 domain"J. Biol. Chem.. 276. 27670-27676 (2001)
[Publications] Fukuda, M. et al.: "The C2A domain of double C2 protein γ contains a functional nuclear localization signal"J. Biol. Chem.. 276. 24441-24444 (2001)
[Publications] Fukami, K.: "Requirement of phospholipase C δ 4 for the Zona pellucida-induced acrosome reaction"science. 292. 920-923 (2001)
[Publications] Suzuki, H. et al.: "Properties of gastric smooth muscles obtained from mice which lack inositol trisphosphate receptor"J. Physiol.. 525. 105-111 (2000)
[Publications] Fujii, S. et al.: "Synaptic plasticity in hippocampal CA1 neurons of mice lacking type 1 inositol-1, 4, 5-trisphosphate receptors"Learning & Memory. 7. 312-320 (2000)
[Publications] Nishiyama, M. et al.: "Calcium stores regulate the polarity and input specificity of synaptic modification."Nature. 408. 584-588 (2000)
[Publications] Fukuda, M. et al.: "Role of the conserved WHXL motif in the C terminus of synaptotagmin in synaptic vesicle docking"Proc. Natl. Acad. Sci.. 97. 14715-14719 (2000)
[Publications] Mikoshiba, K. et al.: "IP_3 Receptor-operated calcium Entry"science {Science's stke(signal Transduction Knowledge Environment) Perspective (Web publication)}. 1-4 (2000)
[Publications] Kume, S. et al.: "Gas family G protein activate IP_3-Ca^<2+> signaling via Gβγ and transduce ventralizing signals in Xenopus"Developmental Biology. 226. 88-103 (2000)
[Publications] Fukuda, M. et al.: "Distinct self-oligomerization activities of synaptotagmin family. -Unique calcium-dependent oligomerization properties of synaptotagmin VII-."J. Biol. Chem.. 275. 28180-28185 (2000)
[Publications] Mizutani, A. et al.: "SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with uniquitous synaptotagmin isoforms"J. Biol. Chem.. 275. 9823-9831 (2000)
[Publications] Ma, H. T. et al.: "Requirement of the inositol trisphosphate receptor for activation of store -operated Ca^<2+> channels"Science. 287. 1647-1651 (2000)

2001 Fiscal Year Annual Research Report

神経可塑性と脳の発生・分化におけるIP_3受容体/Ca^<2+>シグナリングの役割

Principal Investigator

御子柴 克彦 東京大学, 医科学研究所, 教授 (30051840)

Research Products

[Publications] Iwasaki, H. et al.: "2-Aminoethoxydiphenyl Borate (2-APB) Inhibits Capacitative Calcium Entry Independently of the Function of Inositol 1, 4, 5-Trisphosphate Receptors"Receptors & Channels. 7. 429-439 (2001)

[Publications] Fukuda, M. et al.: "Formation of Crystalloid Endoplasmic Recticulum Induced by Expression of Synaptotagmin Lacking the Conserved WHXL Motif in the C Terminus"J. Biol. Chem.. 276. 41112-41119 (2001)

[Publications] Fukuda, M. et al.: "Mechanism of the SDS-resistant Synaptotagmin Clustering Mediated by the Cysteine Cluster at the Interface between the Transmembrane and spacer Domains"J. Biol. Chem.. 276. 40319-40325 (2001)

[Publications] Fukuda, M. et al.: "Mechanism of the calcium-dependent multimerization of synaptotagmin VII mediated by its first and second C2 domain"J. Biol. Chem.. 276. 27670-27676 (2001)

[Publications] Fukuda, M. et al.: "The C2A domain of double C2 protein γ contains a functional nuclear localization signal"J. Biol. Chem.. 276. 24441-24444 (2001)

[Publications] Fukami, K.: "Requirement of phospholipase C δ 4 for the Zona pellucida-induced acrosome reaction"science. 292. 920-923 (2001)

[Publications] Suzuki, H. et al.: "Properties of gastric smooth muscles obtained from mice which lack inositol trisphosphate receptor"J. Physiol.. 525. 105-111 (2000)

[Publications] Fujii, S. et al.: "Synaptic plasticity in hippocampal CA1 neurons of mice lacking type 1 inositol-1, 4, 5-trisphosphate receptors"Learning & Memory. 7. 312-320 (2000)

[Publications] Nishiyama, M. et al.: "Calcium stores regulate the polarity and input specificity of synaptic modification."Nature. 408. 584-588 (2000)

[Publications] Fukuda, M. et al.: "Role of the conserved WHXL motif in the C terminus of synaptotagmin in synaptic vesicle docking"Proc. Natl. Acad. Sci.. 97. 14715-14719 (2000)

[Publications] Mikoshiba, K. et al.: "IP_3 Receptor-operated calcium Entry"science {Science's stke(signal Transduction Knowledge Environment) Perspective (Web publication)}. 1-4 (2000)

[Publications] Kume, S. et al.: "Gas family G protein activate IP_3-Ca^<2+> signaling via Gβγ and transduce ventralizing signals in Xenopus"Developmental Biology. 226. 88-103 (2000)

[Publications] Fukuda, M. et al.: "Distinct self-oligomerization activities of synaptotagmin family. -Unique calcium-dependent oligomerization properties of synaptotagmin VII-."J. Biol. Chem.. 275. 28180-28185 (2000)

[Publications] Mizutani, A. et al.: "SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with uniquitous synaptotagmin isoforms"J. Biol. Chem.. 275. 9823-9831 (2000)

[Publications] Ma, H. T. et al.: "Requirement of the inositol trisphosphate receptor for activation of store -operated Ca^<2+> channels"Science. 287. 1647-1651 (2000)

御子柴克彦東京大学, 医科学研究所, 教授 (30051840)