1998 Fiscal Year Annual Research Report

細胞内情報伝達の生理機能解析と情報分子の可視化

Research Project

Project/Area Number	09273101
Research Institution	The University of Tokyo
Principal Investigator	飯野正光東京大学, 大学院・医学系研究科, 教授 (50133939)
Co-Investigator(Kenkyū-buntansha)	萩原正敏東京医科歯科大, 難治研, 教授 (10208423) 宮崎俊一東京女子医大, 医学部, 教授 (80010081) 河西春郎東京大学, 大学院・医学系研究科, 助教授 (60224375)
Keywords	カルシウム / イノシトール三燐酸 / 膵臓β細胞 / 分泌 / 受精 / 蛍光カルシウム指示薬 / cAMP / GFP
Research Abstract	本研究班は、設計分子の作用を解析するため、収縮、分泌、発生、免疫、転写調節と極めて重要な生体機能を制御するCa^<2+>シグナル機構研究を推進し以下の成果を得た。 ca^<2+>シグナルパターンとIP_3受容体サブタイプの発現パターンの関係を明らかにするため、遺伝子工学手法を援用して単一のIP_3受容体サブタイプのみを発現する細胞系を作成し、各サブタイプの機能を比較した。これによりサブタイプ間には大きな機能的相違が存在し、Ca^<2+>シグナルパターンの違いを形成するのに極めて重要であることを示した。膵臓β細胞では、インスリン顆粒の開口放出にはカルシウム濃度上昇だけでなくAキナーゼによるりん酸化が必要で、それが細胞内ATP濃度に依存的であることを見出した。これがβ細胞のグルコース応答に関与する可能性を示した。受精・初期発生の引き金になる卵細胞内Ca^<2+>濃度上昇を誘発する精子因子の解析を行った.精子抽出物がIP_3受容体を介するCa^<2+>遊離によってCa^<2+>波およびCa^<2+>オシレーションを誘発することを明らかにし、精子細胞質蛋白質の精製に着手した。蛍光波長の異なる2つのGreen Fluorescent Protein(GFP)の蛍光共鳴エネルギー移動が蛋白質の構造変化によって変化し得ることを利用して、細胞内cAMP濃度やCa^<2+>濃度変化のモニターを可能とするような蛋白質の作製に成功した。

Research Products
(25 results)

All Other

All Publications (25 results)

[Publications] Takeshima,H.: "Embryonic lethality and abnomal caridiac myocytes in mice lacking ryanodine receptor type2." EMBO J.17. 3309-3316 (1998)
[Publications] Shimuta,M.: "Structure and expression of mitsugumin29 gene." FEBS Lett.431. 263-267 (1998)
[Publications] Nishi,M.: "Mitsugumin23,a novel transmembrane protein on endoplasmic reticulum and nuclear membrane." FEBS Lett.432. 191-196 (1998)
[Publications] Takeshima,H.: "Mitsugumin29,a novel synaptophysin family member from the triad junction in skeletal muscle." Biochem.J.331. 317-322 (1998)
[Publications] Komazaki,S.: "Morphological abnomalities of adrenal grand and hypertrophy of liver in mutant mice lacking ryanodine receptors." Cell Tissue Res.294. 467-473 (1998)
[Publications] Okada,H.: "Role of the inositol phosphatase SHIP in B cell receptor-induced Ca^<2+> oscillatory response." J.Immunol.161. 5129-5132 (1998)
[Publications] Ikemoto,T.: "Effect of calmodulin on Ca^<2+>-induced Ca^<2+> release of skeletal muscle from mutant mice expressing either ryanodine receptor type 1 or type 3." Pflugers Arch.437. 43-48 (1998)
[Publications] Hirabayashi,T.: "Critical duration of intracellularCa^<2+> response required for continuous translocation and activation of cytosolic phospholipase A_2." J.Biol.Chem.274. 5163-5169 (1999)
[Publications] Hashimot,A.: "Inhibitory modulation of B cell receptor-mediated Ca^<2+> mobilization by SH2 domain containing inositol 5′-phosphatase(SHIP)." J.Biol.Chem.433(in press). (1999)
[Publications] Miyakawa,T.: "Encoding of Ca^<2+> signals by differential expression of IP_3 receptor subtypes." ENBO J.18(in press). (1999)
[Publications] Kasai,H.: "Ca^<2+> dependent exocytosis in endocrine,exocrine and non-secretory cells." Korean J.Physiol.Pharmacol.2. 1-7 (1998)
[Publications] Kasai,H.: "Comparative biology of Ca^<2+>-dependent exocytosis:implications of kinetic diversity for secretory function." Trends Neurosci.22. 88-93 (1999)
[Publications] Takahashi,N.: "Post-priming actions of ATP on Ca^<2+>-dependent exocytosis in pancreatic beta cells." Proc.Natl.Acad.Sci.USA. 96. 760-765 (1999)
[Publications] Kasai,H.: "Multiple components of exocytosis and Ca^<2+> requirements." Phil.Trans.Royal Soc.B. 353. 1-5 (1999)
[Publications] Eto,K.: "Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion." Science. 283. 981-985 (1999)
[Publications] Kyozuka,K.: "Injection of sperm extract mimics spatiotemporal dynamics of Ca^<2+> responses and progression of meiosis at fertilization of ascidian oocytes." Development. 125. 4099-4105 (1998)
[Publications] Sakurai,A.: "Fertilization,embryonic development,and offspring from mouse eggs injected with round spermatids combined with Ca^<2+> oscillation-inducing sperm factor." Mol.Human Reprod.(in press). (1999)
[Publications] Oda,S.: "Spatiotemporal dynamics of the 〔Ca^<2+>〕_i rise induced by microinjection of sperm extract into the mouse egg:preferential induction of a Ca^<2+> wave from the cortex." Dev.Biol.(in press). (1999)
[Publications] Koizumi,J.: "The subcellular localization of SF2/ASF is regulated by the direct interaction with SR protein kinases(SRPKs)." J.Biol.Chem.(in press). (1999)
[Publications] Okamoto,Y.: "cdc2 kinase-mediated phosphorylation of splicing factor SF2/ASF." Biochem.Biophys.Res.Commun.249. 872-878 (1998)
[Publications] Yoshida,K.: "CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells." Mol.Brain Res.57. 241-247 (1998)
[Publications] Shimomura,A.: "Dominant negative ATF1 blocks cyclic AMP-induced neurite outgrowth in PC12D cells." J.Neurochem.70. 1029-1034 (1998)
[Publications] Muro,Y.: "Autoantibody to thioredoxin reductase in an ovarian cancer patient." Biochem.Biophys.Res.Commun.242. 267-271 (1998)
[Publications] Kuroyanagi,N.: "Novel SR-protein-specific kinase,SRPK2,disassembles nuclear speckles." Biochem.Biophys.Res.Commun.242. 357-364 (1998)
[Publications] Kamimoto,T.: "Dymple,a novel dynamin-like high molecular weigt GTPase lacking a proline-rich C-terminal domani in mammalian cells." J.Biol.Chem.273. 1044-1051 (1998)

1998 Fiscal Year Annual Research Report

細胞内情報伝達の生理機能解析と情報分子の可視化

Principal Investigator

飯野 正光 東京大学, 大学院・医学系研究科, 教授 (50133939)

Research Products

[Publications] Takeshima,H.: "Embryonic lethality and abnomal caridiac myocytes in mice lacking ryanodine receptor type2." EMBO J.17. 3309-3316 (1998)

[Publications] Shimuta,M.: "Structure and expression of mitsugumin29 gene." FEBS Lett.431. 263-267 (1998)

[Publications] Nishi,M.: "Mitsugumin23,a novel transmembrane protein on endoplasmic reticulum and nuclear membrane." FEBS Lett.432. 191-196 (1998)

[Publications] Takeshima,H.: "Mitsugumin29,a novel synaptophysin family member from the triad junction in skeletal muscle." Biochem.J.331. 317-322 (1998)

[Publications] Komazaki,S.: "Morphological abnomalities of adrenal grand and hypertrophy of liver in mutant mice lacking ryanodine receptors." Cell Tissue Res.294. 467-473 (1998)

[Publications] Okada,H.: "Role of the inositol phosphatase SHIP in B cell receptor-induced Ca^<2+> oscillatory response." J.Immunol.161. 5129-5132 (1998)

[Publications] Ikemoto,T.: "Effect of calmodulin on Ca^<2+>-induced Ca^<2+> release of skeletal muscle from mutant mice expressing either ryanodine receptor type 1 or type 3." Pflugers Arch.437. 43-48 (1998)

[Publications] Hirabayashi,T.: "Critical duration of intracellularCa^<2+> response required for continuous translocation and activation of cytosolic phospholipase A_2." J.Biol.Chem.274. 5163-5169 (1999)

[Publications] Hashimot,A.: "Inhibitory modulation of B cell receptor-mediated Ca^<2+> mobilization by SH2 domain containing inositol 5′-phosphatase(SHIP)." J.Biol.Chem.433(in press). (1999)

[Publications] Miyakawa,T.: "Encoding of Ca^<2+> signals by differential expression of IP_3 receptor subtypes." ENBO J.18(in press). (1999)

[Publications] Kasai,H.: "Ca^<2+> dependent exocytosis in endocrine,exocrine and non-secretory cells." Korean J.Physiol.Pharmacol.2. 1-7 (1998)

[Publications] Kasai,H.: "Comparative biology of Ca^<2+>-dependent exocytosis:implications of kinetic diversity for secretory function." Trends Neurosci.22. 88-93 (1999)

[Publications] Takahashi,N.: "Post-priming actions of ATP on Ca^<2+>-dependent exocytosis in pancreatic beta cells." Proc.Natl.Acad.Sci.USA. 96. 760-765 (1999)

[Publications] Kasai,H.: "Multiple components of exocytosis and Ca^<2+> requirements." Phil.Trans.Royal Soc.B. 353. 1-5 (1999)

[Publications] Eto,K.: "Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion." Science. 283. 981-985 (1999)

[Publications] Kyozuka,K.: "Injection of sperm extract mimics spatiotemporal dynamics of Ca^<2+> responses and progression of meiosis at fertilization of ascidian oocytes." Development. 125. 4099-4105 (1998)

[Publications] Sakurai,A.: "Fertilization,embryonic development,and offspring from mouse eggs injected with round spermatids combined with Ca^<2+> oscillation-inducing sperm factor." Mol.Human Reprod.(in press). (1999)

[Publications] Oda,S.: "Spatiotemporal dynamics of the 〔Ca^<2+>〕_i rise induced by microinjection of sperm extract into the mouse egg:preferential induction of a Ca^<2+> wave from the cortex." Dev.Biol.(in press). (1999)

[Publications] Koizumi,J.: "The subcellular localization of SF2/ASF is regulated by the direct interaction with SR protein kinases(SRPKs)." J.Biol.Chem.(in press). (1999)

[Publications] Okamoto,Y.: "cdc2 kinase-mediated phosphorylation of splicing factor SF2/ASF." Biochem.Biophys.Res.Commun.249. 872-878 (1998)

[Publications] Yoshida,K.: "CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells." Mol.Brain Res.57. 241-247 (1998)

[Publications] Shimomura,A.: "Dominant negative ATF1 blocks cyclic AMP-induced neurite outgrowth in PC12D cells." J.Neurochem.70. 1029-1034 (1998)

[Publications] Muro,Y.: "Autoantibody to thioredoxin reductase in an ovarian cancer patient." Biochem.Biophys.Res.Commun.242. 267-271 (1998)

[Publications] Kuroyanagi,N.: "Novel SR-protein-specific kinase,SRPK2,disassembles nuclear speckles." Biochem.Biophys.Res.Commun.242. 357-364 (1998)

[Publications] Kamimoto,T.: "Dymple,a novel dynamin-like high molecular weigt GTPase lacking a proline-rich C-terminal domani in mammalian cells." J.Biol.Chem.273. 1044-1051 (1998)

飯野正光東京大学, 大学院・医学系研究科, 教授 (50133939)