1997 年度実績報告書

IP_3受容体の細胞内Ca^<2+>制御機構と情報伝達及び発生・分化と可塑性における役割

研究課題

研究課題/領域番号	09308030
研究種目	基盤研究(A)
研究機関	東京大学
研究代表者	御子柴克彦東京大学, 医科学研究所, 教授 (30051840)
研究分担者	道川貴章東京大学, 医科学研究所, 助手 (90282516) 井上貴文東京大学, 医科学研究所, 助手 (10262081) 古市貞一東京大学, 医科学研究所, 助教授 (50219094)
キーワード	IP_3 / IP_3受容体 / カルシウム / 背側化 / 腹側化 / 二次軸形成 / BMP4 / IP_3誘導カルシウム放出
研究概要	IP_3受容体は細胞内小胞体上に存在するIP_3依存的に開口するCa^<2+>チャンネルである。申請者は、IP_3受容体の欠損マウスを作製した。このマウスは出生率が5分の1に減少し、かつ出生したものでもけいれんや運動失調を引き起こし、25日までに全例死亡することを明らかにした。初期胚発生において、フォスファチヂルイノシトール(PI)代謝回転を阻害するLiClが、二次胚形成を誘導し、細胞内イノシトール3リン酸(IP3)の濃度を減少させることが知られており、初期胚発生において重要な役割を担うことが考えられている。申請者は、初期胚の形態形成の分子機構を明らかにするために、アフリカツメガエルの系を用いて、PIシグナル伝達系に焦点を絞り、胚発生における作用機構を詳細に検討するため、IP_3受容体に対する特異的阻害活性をもつモノクロール抗体を単離した。初期胚で強制発現したmAChRに対するアゴニスト依存的なカルシウム遊離の阻害を指標でアッセイしたところ、これらの複数のIP_3受容体モノクローナル抗体はそれぞれカルシウム遊離の阻害活性の程度が異なることが分かった。これらモノクロール抗体をアフリカツメガエル初期胚に微小注入したところ、4細胞期の割球への注入により特異的に二次軸が生成された。同じ抗体量による二次軸誘導能はものクロール抗体のIP_3依存性Ca^<2+>放出阻害活性に相関していることにより、IP_3/Ca^<2+>伝達系は背側化シグナルを伝達することが強く示唆された。

研究成果
(33件)

すべてその他

すべて文献書誌 (33件)

[文献書誌] Del Rio,J.A: "A role for Cajal-Retzius cells and reelin in the developement of hippocampal connections." Nature.385. 70-74 (1997)
[文献書誌] Umemori,H.: "Activation of the G Protein Gq/11 through tyrosine phosphorylation of the a subunit." Science.276. 1878-1882 (1997)
[文献書誌] Sheldon,M.: "Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice." Nature.389.730-733 (1997)
[文献書誌] Kume,S: "Role of Inositol 1,4,5-Trisphosphate Receptor in Ventral Signaling in Xenopus Embryos." Science.278.1940-1943 (1997)
[文献書誌] Zhao,H.: "Functional expression of a mammalian odorant receptor." Science.279. 237-242 (1998)
[文献書誌] D'Arcangelo,G: "Reelin is a secred glycoprotein recognized by the CR-50 monoclonal antibody." J.Neurosci..17.23-31 (1997)
[文献書誌] Ohara-ImaizumiM: "Distinct roles of C2A and C2B domains of synaptotagmin in the regulation of exocytosis in adrenal chromaffin cells." Proc.Natl.Acad.Sci.USA.94.287-291 (1997)
[文献書誌] Kume,S: "Developmental Expression of the Inositol 1,4,5-Trisphosphate Receptor and Structural Changes in the Endoplasmic Reticulum during Oogenesis and Meiotic Maturation of Xenopus laevis." Developmental Biology.182.228-239 (1997)
[文献書誌] Mehrotra,B: "Selective photoaffinity labeling of the inositol polyphosphate binding C2B domains of synaptotagmins." J.Biol.Chem.272.4237-4244 (1997)
[文献書誌] Morita,N: "Astrocytic Lineage Analysis by Detection of GFAP Promoter Activity in vitro." Developmental Neuroscience.19.210-218 (1997)
[文献書誌] Sayers,L.G: "Intracellular targeting and homotetramer formation of a truncated inositol 1,4,5-trisphosphatereceptor/green fluorescent protein chimera in Xenopus leavis oocytes." Biochem.J.323.273-280 (1997)
[文献書誌] Nagai,T.: "The expression of the mouse Zic 1,Zic 2,and Zic 3 gene suggests an essential role for Zic genes in body pattern formation." Developmental Biology.182.299-313 (1997)
[文献書誌] Yoneshima,H.: "Ca2+ differetly regulates the ligand-affinity ststes of type 1 and type 3 inositol 1,4,5-trisphosphate receptors." Biochem.J.322.591-596 (1997)
[文献書誌] Tovey.S.C: "Identification and characerization of inositol 1,4,5-trisphosphate receprors in the rat testis." Cell Calcium.21.311-319 (1997)
[文献書誌] Hisatsume,C.: "Phosphorylation-dependent Regulation of N-Methy1-D-asparate Receptors by calmodulin." J.Biol.Cehm.272.20805-20810 (1997)
[文献書誌] Maruyama,T.: "2APB,2-aminoethoxydiphenyl borate,a membrance penetrable modulator of Ins (1,4,5) P3-induced Ca2+ release." J.Biochem.122.498-505 (1997)
[文献書誌] Maruyama,T.: "Attenuation of intracellular Ca2+ and secretory responses by Ins (1,4,5) P3-induced Ca2+ release modulator,2APB,in rat pancreatic acinar cells." Biomedical Research.18. 297-302 (1997)
[文献書誌] Kume,S.: "Developmental expression of the inositol 1,4,5-trisphosphate receptor and localization of inositol 1,4,5-trisphosphate during early embryogenesis in Xenopus laevis." Mechanisms of Development.66.157-168 (1997)
[文献書誌] Nakata,K.: "Xenopus Zic3,a primary regulator both in neural and neural crest development." Proc.Natl.Acad Sci.94.11980-11985 (1997)
[文献書誌] Morikawa,K.: "Transcription Initiation Sites and Promoter Structure of the Mouse Type 2 Inositol 1,4,5-Trisphospharate Receptor Gene." Gene.196.181-185 (1997)
[文献書誌] Wada,E.: "Generation and Characterization of Mice Lacking Gastrin-Releasing Peptide Receptor." Biochem.Biophys.Res.Comm.239.28-33 (1997)
[文献書誌] Taketo,M.: "Inositol-1,3,4,5-tetrakisphosphate Binding Sites in Control and ras-Transformed NIH/3T3 Fibroblasts." Biochem.Biophys.Res.Commun.239. 349-352 (1997)
[文献書誌] Lang,E.J: "The first C2 domain of synaptotagmin is required for exocytosis of Insulin from pancreatic b-cells : action of synaptotagmin at low micromolar calcium." EMBO J.16.5837-5846 (1997)
[文献書誌] Yoneshima,H.: "A novel neurological mutant mouse,yotari,which exhibits reeler-like phenotype but expresses CR-50 antigen/Reelin." Neuroscience Research.29.217-223 (1997)
[文献書誌] Tamura,H.: "High sulfotransferase activity for phenolic aromatic odorants present in the mouse olfactory." Chemico-Biological Interactions.104.1-9 (1997)
[文献書誌] Miyata,T.: "Regulation of Purkinje Cell Alignment by Reelin as Revealed with CR-50 Antibody." J.Neurosci.17.3599-3609 (1997)
[文献書誌] Nakayama,T: "Mapping of the Human HPC-1/Syntaxin 1A Gene (STX1A) to Chromosome 7 Band q11.2." Genomics.42.173-176 (1997)
[文献書誌] Fukuda,M: "Regulation by bivalent cations of phospholipid binding to the C2A domain of synaptotagmin III." Biochem.J.323. 421-425 (1997)
[文献書誌] Mochida,S.: "Roles of Synaptotagmin C2 Domains in Neurotransmitter secretion and inositol high-polyphosphate binding at mammalian cholinergic synapses." Neurosci.77. 937-943 (1997)
[文献書誌] Nakajima,K: "Distruption of hippocampal development in vivo by CR-50 mAb against reelin." Proc.Natl.Acad.Sci.94. 8196-8201 (1997)
[文献書誌] Konishi,Y: "Demonstration of an E-box and transcriptional regulation of the mouse type 1 Inositol 1,4,5-trisphosphate receptor gene." J.Neurochem.69. 476-484 (1997)
[文献書誌] Kojima,T.: "Characterization of the pleckstrin homology domain of Btk as an Inositol polyphosphate and phosphoinositide binding domain." Biochem.Biophys.Res.Comm.236. 333-339 (1997)
[文献書誌] Tamura,H.: "High sulfotransferase activity for phenolic aromatic odorants present in the mouse olfactory organ." Chemico-Biological Interactions.104.1-9 (1997)

1997 年度 実績報告書

IP_3受容体の細胞内Ca^<2+>制御機構と情報伝達及び発生・分化と可塑性における役割

研究代表者

御子柴 克彦 東京大学, 医科学研究所, 教授 (30051840)

研究成果

[文献書誌] Del Rio,J.A: "A role for Cajal-Retzius cells and reelin in the developement of hippocampal connections." Nature.385. 70-74 (1997)

[文献書誌] Umemori,H.: "Activation of the G Protein Gq/11 through tyrosine phosphorylation of the a subunit." Science.276. 1878-1882 (1997)

[文献書誌] Sheldon,M.: "Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice." Nature.389.730-733 (1997)

[文献書誌] Kume,S: "Role of Inositol 1,4,5-Trisphosphate Receptor in Ventral Signaling in Xenopus Embryos." Science.278.1940-1943 (1997)

[文献書誌] Zhao,H.: "Functional expression of a mammalian odorant receptor." Science.279. 237-242 (1998)

[文献書誌] D'Arcangelo,G: "Reelin is a secred glycoprotein recognized by the CR-50 monoclonal antibody." J.Neurosci..17.23-31 (1997)

[文献書誌] Ohara-ImaizumiM: "Distinct roles of C2A and C2B domains of synaptotagmin in the regulation of exocytosis in adrenal chromaffin cells." Proc.Natl.Acad.Sci.USA.94.287-291 (1997)

[文献書誌] Kume,S: "Developmental Expression of the Inositol 1,4,5-Trisphosphate Receptor and Structural Changes in the Endoplasmic Reticulum during Oogenesis and Meiotic Maturation of Xenopus laevis." Developmental Biology.182.228-239 (1997)

[文献書誌] Mehrotra,B: "Selective photoaffinity labeling of the inositol polyphosphate binding C2B domains of synaptotagmins." J.Biol.Chem.272.4237-4244 (1997)

[文献書誌] Morita,N: "Astrocytic Lineage Analysis by Detection of GFAP Promoter Activity in vitro." Developmental Neuroscience.19.210-218 (1997)

[文献書誌] Sayers,L.G: "Intracellular targeting and homotetramer formation of a truncated inositol 1,4,5-trisphosphatereceptor/green fluorescent protein chimera in Xenopus leavis oocytes." Biochem.J.323.273-280 (1997)

[文献書誌] Nagai,T.: "The expression of the mouse Zic 1,Zic 2,and Zic 3 gene suggests an essential role for Zic genes in body pattern formation." Developmental Biology.182.299-313 (1997)

[文献書誌] Yoneshima,H.: "Ca2+ differetly regulates the ligand-affinity ststes of type 1 and type 3 inositol 1,4,5-trisphosphate receptors." Biochem.J.322.591-596 (1997)

[文献書誌] Tovey.S.C: "Identification and characerization of inositol 1,4,5-trisphosphate receprors in the rat testis." Cell Calcium.21.311-319 (1997)

[文献書誌] Hisatsume,C.: "Phosphorylation-dependent Regulation of N-Methy1-D-asparate Receptors by calmodulin." J.Biol.Cehm.272.20805-20810 (1997)

[文献書誌] Maruyama,T.: "2APB,2-aminoethoxydiphenyl borate,a membrance penetrable modulator of Ins (1,4,5) P3-induced Ca2+ release." J.Biochem.122.498-505 (1997)

[文献書誌] Maruyama,T.: "Attenuation of intracellular Ca2+ and secretory responses by Ins (1,4,5) P3-induced Ca2+ release modulator,2APB,in rat pancreatic acinar cells." Biomedical Research.18. 297-302 (1997)

[文献書誌] Kume,S.: "Developmental expression of the inositol 1,4,5-trisphosphate receptor and localization of inositol 1,4,5-trisphosphate during early embryogenesis in Xenopus laevis." Mechanisms of Development.66.157-168 (1997)

[文献書誌] Nakata,K.: "Xenopus Zic3,a primary regulator both in neural and neural crest development." Proc.Natl.Acad Sci.94.11980-11985 (1997)

[文献書誌] Morikawa,K.: "Transcription Initiation Sites and Promoter Structure of the Mouse Type 2 Inositol 1,4,5-Trisphospharate Receptor Gene." Gene.196.181-185 (1997)

[文献書誌] Wada,E.: "Generation and Characterization of Mice Lacking Gastrin-Releasing Peptide Receptor." Biochem.Biophys.Res.Comm.239.28-33 (1997)

[文献書誌] Taketo,M.: "Inositol-1,3,4,5-tetrakisphosphate Binding Sites in Control and ras-Transformed NIH/3T3 Fibroblasts." Biochem.Biophys.Res.Commun.239. 349-352 (1997)

[文献書誌] Lang,E.J: "The first C2 domain of synaptotagmin is required for exocytosis of Insulin from pancreatic b-cells : action of synaptotagmin at low micromolar calcium." EMBO J.16.5837-5846 (1997)

[文献書誌] Yoneshima,H.: "A novel neurological mutant mouse,yotari,which exhibits reeler-like phenotype but expresses CR-50 antigen/Reelin." Neuroscience Research.29.217-223 (1997)

[文献書誌] Tamura,H.: "High sulfotransferase activity for phenolic aromatic odorants present in the mouse olfactory." Chemico-Biological Interactions.104.1-9 (1997)

[文献書誌] Miyata,T.: "Regulation of Purkinje Cell Alignment by Reelin as Revealed with CR-50 Antibody." J.Neurosci.17.3599-3609 (1997)

[文献書誌] Nakayama,T: "Mapping of the Human HPC-1/Syntaxin 1A Gene (STX1A) to Chromosome 7 Band q11.2." Genomics.42.173-176 (1997)

[文献書誌] Fukuda,M: "Regulation by bivalent cations of phospholipid binding to the C2A domain of synaptotagmin III." Biochem.J.323. 421-425 (1997)

[文献書誌] Mochida,S.: "Roles of Synaptotagmin C2 Domains in Neurotransmitter secretion and inositol high-polyphosphate binding at mammalian cholinergic synapses." Neurosci.77. 937-943 (1997)

[文献書誌] Nakajima,K: "Distruption of hippocampal development in vivo by CR-50 mAb against reelin." Proc.Natl.Acad.Sci.94. 8196-8201 (1997)

[文献書誌] Konishi,Y: "Demonstration of an E-box and transcriptional regulation of the mouse type 1 Inositol 1,4,5-trisphosphate receptor gene." J.Neurochem.69. 476-484 (1997)

[文献書誌] Kojima,T.: "Characterization of the pleckstrin homology domain of Btk as an Inositol polyphosphate and phosphoinositide binding domain." Biochem.Biophys.Res.Comm.236. 333-339 (1997)

[文献書誌] Tamura,H.: "High sulfotransferase activity for phenolic aromatic odorants present in the mouse olfactory organ." Chemico-Biological Interactions.104.1-9 (1997)

1997 年度実績報告書

御子柴克彦東京大学, 医科学研究所, 教授 (30051840)