2001 Fiscal Year Annual Research Report

IP_3受容体のIP_3シグナル分子認識機構の解明と応用

Research Project

Project/Area Number	13357001
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 / IP_3レセプター / カルシウム / IP_3スポンジ
Research Abstract	IP_3レセプターはIP_3をリガンドとして、カルシウム存在下で開口するカルシウムチャネルである。通常一つのチャネルの活性を1とした場合、結合領域を決めたとしても活性は同じ値であるにもかかわらず、IP_3レセプター内のIP_3結合領域を同定したところ、その結合活性は500〜1000倍も高い値を示した。詳細な解析をしたところ、N末端より223アミノ酸残基までが抑制領域として活性の制御にかかわり、226残基より、576残基までが500〜1000倍結合親和性の高いIP_3結合のコアー配列を有していることが明らかとなった。このうち、265アミノ酸残基目のプルギニン、508残基目のリジン、511残基日のアルギニンが結合に必須で、そのうちの一つのアミノ酸でも変異すると結合を失うことを明らかにした。このIP_3認識配列を用いて、224-604残基にGST配列を結合することにより安定なIP_3吸着剤(IP_3スポンジと命名)開発することに成功した。このIP_3スポンジを用いることにより、細胞内のIP_3が細胞機能にどのような役割をしているかを受精現象に適用した。ヒトデの受精時には、卵に精子が結合することにより受精膜の形成がおこり、多重精子現象を阻害する。卵にIP_3スポンジをあらかじめ注入しておくと、受精膜の形成が阻害されていた。

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 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 pellucidainduced 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.: "Gαs 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 calciurm-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

IP_3受容体のIP_3シグナル分子認識機構の解明と応用

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 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 pellucidainduced 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.: "Gαs 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 calciurm-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)