2002 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	背腹軸形成 / IP_3レセプター / GSK3β / NF-AT / カルシウム / Wntシグナリング
Research Abstract	脳神経系の発生分化の研究に於いて背腹軸の決定は重要である。これまでに多くの背側化因子および腹側化因子が同定されているが、いずれもIP_3-Ca^<2+>シグナル伝達経路との関連は明らかでなかった。Wnt経路は現在のところその機能から二つのグループ、背側化活性を持つWnt/β-catenin、Gタンパク質を介してCa^<2+>動員を起こすとされるWnt/Ca^<2+>経路の二つに分けられる。そこで脊椎動物初期発生における体軸形成の分子機構を明らかにするために、IP_3-Ca^<2+>シグナル伝達経路の上流のシグナル、つまりIP3産生を誘導する分子、および下流のシグナルである、IP_3により上昇した細胞質Ca^<2+>により制御され腹側化を誘導する分子の同定を試みた。既にIP3レセプターが腹側化に重要であることを報告したが(Science1997)、今回は転写因子の1つであるnuclear factor of activated T-cell(NF-AT)が受精後、4細胞期に腹側化因子であることを同定した。更にWnt/β-catenin経路を少なくともGSK3βより上流、Xdshより下流で負に制御していることを明らかにした。Wnt/β-catenin経路との作用点がどこかをXNF-AT ΔRelとWnt経路の負の調節因子(GSK3βなど)との共発現により解析した。XNF-ATドミナントネガティブフォームによるsiamois, Xnr3の発現誘導はXGSK3βによって消失した。この結果はXNF-AT経路はWnt/β-catenin経路を少なくともGSK3βより上流で負に制御していることを示唆した。

Research Products

(31 results)

All Other

All Publications (31 results)

[Publications] Iwasaki Hirohide: "Molecular Characterization of the Starfish Inositol 1,4,5-Trisphosphate Receptor and Its Role during Oocyte Maturation and Fertilization"J.Biol.Chem. 277(4). 2763-2772 (2002)
[Publications] Yokoyama, Kazumasa: "BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP_3 receptor"EMBO.J.. 21. 83-92 (2002)
[Publications] Nagai, Takeharu: "A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications"Nat.Biotechnol.. 20. 87-90 (2002)
[Publications] Els den Dekker: "Cyclic AMP Raises Intracellular Ca^<2+>in Human Megakaryocytes Independent of Protein Kinase A"Arterioscler Thromb Vasc Biol.. 22. 179-186 (2002)
[Publications] Uchiyama Tsuyoshi: "Anovel recombinant hyper-affinity Insitol 1,4,5-trisphosphate(IP_3)absorbent traps IP_3,resulting in specific inhibition of IP_3-mediated calcium signaling"J.Biol.Chem. 277(10). 8106-8113 (2002)
[Publications] Fukuda Mitsunori: "Synaptotagmin IX regulates Ca^<2+>-dependent secretion in PC12 cells"J.Biol.Chem.. 277(7). 4601-4604 (2002)
[Publications] Aruga Jun: "Zic2 controls cerebellar development in cooperation with zicl"J.Neurosci.. 22(1). 218-225 (2002)
[Publications] Saneyoshi Takeo: "The Wnt/Calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos"Nature. 417. 295-299 (2002)
[Publications] Taruho S.Kuroda: "The Slp Homology Domain of Synaptotagmin-like Proteins 1-4 and Slac2 Functions as a Novel Rab27A Binding Domain"J.Biol.Chem. 277(11). 9212-9218 (2002)
[Publications] Fukuda Mitsunori: "Slac2-a/melanophilin, the Missing Link Between Rab27 and Myosin Va : Implications of a Tripartite Protein Complex for Melanosome Transport"J.Biol.Chem.. 277(14). 12432-12436 (2002)
[Publications] Matsu-ura Toru: "Seizure-mediated accumulation of the β subunit or Ca^<2+> /calmodulin-dependent protein kinase II in nuclei of mouse brain cells"Neurosci.Lett.. 322. 149-152 (2002)
[Publications] Ohshima Toshio: "Cdk5/p35 contributes synergistically with Reelin/Dab1 to the positioning of facial branchiomotor and inferior olive neurons in the developing mouse hindbrain"J.Neurosci.. 22(10). 4036-4044 (2002)
[Publications] Konishi Y.: "Basic Helix-Loop-Helix(bHLH)Transcription Factors in the Nervous System"Curr.Topics in Neurochem.. (in press). (2002)
[Publications] Tamura Taka-aki: "Neural Activity-Inducible Transcription Factors : Identification of Ca^<2+>-Related Transcriptional Regulators Induced in the Mouse Brain Following Pentylenetetrazol-Mediated Seizure"Recent Res.Devel.Mol.Cell.Biol.. 3. 75-86 (2002)
[Publications] Taruho S.Kuroda: "Synaptotagmin-like protein 5 : a novel Rab27A effector with C-terminal tandem C2 domais"Biochem.Biophys.Res.Commun. 293. 899-906 (2002)
[Publications] Kitaguchi Tetsuya: "Xenopus Brachyury regulates mesodermal expression of Zic3, a gene controlling left-riht asymmetry"Develop.Growth Differ. 44. 55-61 (2002)
[Publications] Hamada Kozo: "Two-state Changes in Inositol 1,4,5-Trisphosphate Receptor Regulated by Calcium"J.Biol.Chem.. 277(24). 21115-21118 (2002)
[Publications] Saegusa Chika: "Synaptotagmin V Is Targeted to Dense-core Vesicles That Undergo Caalcium-dependent Exocytosis in PC12 Cells"J.Biol.Chem. 277(27). 24499-24505 (2002)
[Publications] Sheng-Tian Li.: "Calcineurin Plays Different Roles in Group II Metabotropic Glutamate Receptor-and NMDA Receptor-Dependent Long-Term Depression"J.Neurosci.. 22(12). 5034-5041 (2002)
[Publications] Fukuda Mitsunori: "Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human"Biochem J.. 365. 173-180 (2002)
[Publications] Ibata Keiji: "Non-polarized distribution of synaptotagmin IV in neurons : evidence that synaptotagmin IV is not a synaptic vesicle protein"Neurosci.R.. 43. 401-406 (2002)
[Publications] Fukuda Mitsunori: "The Calcium-binding Loops of the Tandem C2 Domains of Synaptotagmin VII Cooperatively Mediate Calcium-dependent Oligomerization"J.Biol.Chem.. 277(32). 29315-29320 (2002)
[Publications] Hayashi Kanehiro: "Pak1 Is Involved in Dendrite Initiation as a Downstream Effector of Rac1 in Cortical Neurons"Mol.Cell.Neuro. 20. 579-594 (2002)
[Publications] M.Salanova: "Homer proteins and InsP_3 receptors co-localise in the longitudinal sarcoplasmic reticulum of skeletal muscle fibres"Cell Calcium. 32(4). 193-200 (2002)
[Publications] Ivan Bosanac: "Structure of the inositol 1,4,5-trisphoshate receptor binding core in complex with IP_3"Nature. (in press). (2002)
[Publications] Ohshima Toshio: "Reelin Signaling and Cdk5 in the control of Neuronal Positioning"Molecular Neurobiology. 26(2-3). 153-166 (2002)
[Publications] Shiro Suetsugu: "Sustained Activation of N-WASP through Phosphorylation Is Essential for Neurite Extension"Developmental Cell. 3. 645-658 (2002)
[Publications] Ogura Hiroo: "Neurotoxic Damage of Granule Cells in the Dentate Gyrus and the Cerebellum and Congnitive Deficit Following Neonatal Administration of Phenytoin in Mice"J.Neuropathology and Experimental Neurology. 61. 956-967 (2002)
[Publications] Matsu-ura Toru.: "Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain"Brain Res.Mol.Brain Res.. 109(1-2). 198-206 (2002)
[Publications] Songbai Zhang: "Protein 4.1N Is Required for Translocation of Inositol 1,4,5-Trisphosphate Receptor Type 1 to the Basolateral Membrane Domain in Polarized Madin-Darby Canine Kidney Cell"J.Biol.Chem.. 278(6). 4048-4056 (2003)
[Publications] Ando Hideaki: "IRBIT, a Novel Inositol 1,4,5-Trisphosphate (IP_3)Receptor Binding Protein, Is Released from the IP_3 Receptor upon IP_3 Binding to the Receptor"J.Biol.Chem.. (in press). (2003)

2002 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 Hirohide: "Molecular Characterization of the Starfish Inositol 1,4,5-Trisphosphate Receptor and Its Role during Oocyte Maturation and Fertilization"J.Biol.Chem. 277(4). 2763-2772 (2002)

[Publications] Yokoyama, Kazumasa: "BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP_3 receptor"EMBO.J.. 21. 83-92 (2002)

[Publications] Nagai, Takeharu: "A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications"Nat.Biotechnol.. 20. 87-90 (2002)

[Publications] Els den Dekker: "Cyclic AMP Raises Intracellular Ca^<2+>in Human Megakaryocytes Independent of Protein Kinase A"Arterioscler Thromb Vasc Biol.. 22. 179-186 (2002)

[Publications] Uchiyama Tsuyoshi: "Anovel recombinant hyper-affinity Insitol 1,4,5-trisphosphate(IP_3)absorbent traps IP_3,resulting in specific inhibition of IP_3-mediated calcium signaling"J.Biol.Chem. 277(10). 8106-8113 (2002)

[Publications] Fukuda Mitsunori: "Synaptotagmin IX regulates Ca^<2+>-dependent secretion in PC12 cells"J.Biol.Chem.. 277(7). 4601-4604 (2002)

[Publications] Aruga Jun: "Zic2 controls cerebellar development in cooperation with zicl"J.Neurosci.. 22(1). 218-225 (2002)

[Publications] Saneyoshi Takeo: "The Wnt/Calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos"Nature. 417. 295-299 (2002)

[Publications] Taruho S.Kuroda: "The Slp Homology Domain of Synaptotagmin-like Proteins 1-4 and Slac2 Functions as a Novel Rab27A Binding Domain"J.Biol.Chem. 277(11). 9212-9218 (2002)

[Publications] Fukuda Mitsunori: "Slac2-a/melanophilin, the Missing Link Between Rab27 and Myosin Va : Implications of a Tripartite Protein Complex for Melanosome Transport"J.Biol.Chem.. 277(14). 12432-12436 (2002)

[Publications] Matsu-ura Toru: "Seizure-mediated accumulation of the β subunit or Ca^<2+> /calmodulin-dependent protein kinase II in nuclei of mouse brain cells"Neurosci.Lett.. 322. 149-152 (2002)

[Publications] Ohshima Toshio: "Cdk5/p35 contributes synergistically with Reelin/Dab1 to the positioning of facial branchiomotor and inferior olive neurons in the developing mouse hindbrain"J.Neurosci.. 22(10). 4036-4044 (2002)

[Publications] Konishi Y.: "Basic Helix-Loop-Helix(bHLH)Transcription Factors in the Nervous System"Curr.Topics in Neurochem.. (in press). (2002)

[Publications] Tamura Taka-aki: "Neural Activity-Inducible Transcription Factors : Identification of Ca^<2+>-Related Transcriptional Regulators Induced in the Mouse Brain Following Pentylenetetrazol-Mediated Seizure"Recent Res.Devel.Mol.Cell.Biol.. 3. 75-86 (2002)

[Publications] Taruho S.Kuroda: "Synaptotagmin-like protein 5 : a novel Rab27A effector with C-terminal tandem C2 domais"Biochem.Biophys.Res.Commun. 293. 899-906 (2002)

[Publications] Kitaguchi Tetsuya: "Xenopus Brachyury regulates mesodermal expression of Zic3, a gene controlling left-riht asymmetry"Develop.Growth Differ. 44. 55-61 (2002)

[Publications] Hamada Kozo: "Two-state Changes in Inositol 1,4,5-Trisphosphate Receptor Regulated by Calcium"J.Biol.Chem.. 277(24). 21115-21118 (2002)

[Publications] Saegusa Chika: "Synaptotagmin V Is Targeted to Dense-core Vesicles That Undergo Caalcium-dependent Exocytosis in PC12 Cells"J.Biol.Chem. 277(27). 24499-24505 (2002)

[Publications] Sheng-Tian Li.: "Calcineurin Plays Different Roles in Group II Metabotropic Glutamate Receptor-and NMDA Receptor-Dependent Long-Term Depression"J.Neurosci.. 22(12). 5034-5041 (2002)

[Publications] Fukuda Mitsunori: "Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human"Biochem J.. 365. 173-180 (2002)

[Publications] Ibata Keiji: "Non-polarized distribution of synaptotagmin IV in neurons : evidence that synaptotagmin IV is not a synaptic vesicle protein"Neurosci.R.. 43. 401-406 (2002)

[Publications] Fukuda Mitsunori: "The Calcium-binding Loops of the Tandem C2 Domains of Synaptotagmin VII Cooperatively Mediate Calcium-dependent Oligomerization"J.Biol.Chem.. 277(32). 29315-29320 (2002)

[Publications] Hayashi Kanehiro: "Pak1 Is Involved in Dendrite Initiation as a Downstream Effector of Rac1 in Cortical Neurons"Mol.Cell.Neuro. 20. 579-594 (2002)

[Publications] M.Salanova: "Homer proteins and InsP_3 receptors co-localise in the longitudinal sarcoplasmic reticulum of skeletal muscle fibres"Cell Calcium. 32(4). 193-200 (2002)

[Publications] Ivan Bosanac: "Structure of the inositol 1,4,5-trisphoshate receptor binding core in complex with IP_3"Nature. (in press). (2002)

[Publications] Ohshima Toshio: "Reelin Signaling and Cdk5 in the control of Neuronal Positioning"Molecular Neurobiology. 26(2-3). 153-166 (2002)

[Publications] Shiro Suetsugu: "Sustained Activation of N-WASP through Phosphorylation Is Essential for Neurite Extension"Developmental Cell. 3. 645-658 (2002)

[Publications] Ogura Hiroo: "Neurotoxic Damage of Granule Cells in the Dentate Gyrus and the Cerebellum and Congnitive Deficit Following Neonatal Administration of Phenytoin in Mice"J.Neuropathology and Experimental Neurology. 61. 956-967 (2002)

[Publications] Matsu-ura Toru.: "Seizure-mediated neuronal activation induces DREAM gene expression in the mouse brain"Brain Res.Mol.Brain Res.. 109(1-2). 198-206 (2002)

[Publications] Songbai Zhang: "Protein 4.1N Is Required for Translocation of Inositol 1,4,5-Trisphosphate Receptor Type 1 to the Basolateral Membrane Domain in Polarized Madin-Darby Canine Kidney Cell"J.Biol.Chem.. 278(6). 4048-4056 (2003)

[Publications] Ando Hideaki: "IRBIT, a Novel Inositol 1,4,5-Trisphosphate (IP_3)Receptor Binding Protein, Is Released from the IP_3 Receptor upon IP_3 Binding to the Receptor"J.Biol.Chem.. (in press). (2003)

御子柴克彦東京大学, 医科学研究所, 教授 (30051840)