1997 年度実績報告書

細胞内情報伝達の生理機能解析と情報分子の可視化

研究課題

研究課題/領域番号	09273101
研究種目	重点領域研究
研究機関	東京大学
研究代表者	飯野正光東京大学, 大学院・医学系研究科, 教授 (50133939)
研究分担者	萩原正敏東京医科歯科大学, 難治疾患研究所, 教授 (10208423) 宮崎俊一東京女子医科大学, 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)
キーワード	血管平滑筋 / カルシウム / イノシトール三燐酸 / 分泌 / 受精 / 蛍光カルシウム指示薬 / 転写制御
研究概要	本研究班は、設計分子の作用を解析するため、循環、分泌、発生、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。共焦点顕微鏡法を用い血管組織において細胞レベルの相互作用解析に成功した。これにより、内皮細胞のCa^<2+>オシレーションが一酸化窒素を介して平滑筋細胞のCa^<2+>オシレーション頻度を制御し、血圧制御に関わることを明らかにした。また、ケイジド試薬を用いて定量的開口放出過程解析を行い、開口放出速度はCa^<2+>濃度のみならず分泌細胞の種類によって著しく異なることを示した。また、脾β細胞においてインシュリン顆粒に2種類の分泌様式があること、その内、速い分泌にはCa^<2+>と同様にりん酸化が分泌の最終的トリガーとなり、それにより細胞内ATP濃度感受性の分泌が成されていることを見出した。受精においては、精子細胞質蛋白質に卵細胞内Ca^<2+>濃度の上昇を誘発する因子があることを明らかにし、この精製を試みつつある。マウス未熟精子細胞の卵内注入によっても、IP_3受容体アゴニストの同時注入によって人為的にCa^<2+>オシレーションを起すと、卵は受精し、2細胞胚を宿主母体に移植して正常な産仔が得られることを明らかにした。転写制御に関わるSF2結合能を有するタンパク質リン酸化酵素を発見し精製した。今後、特異的阻害剤を検索し、この酵素が選択的スプライシング機構においてどのような意義を持つのかを明らかにしていきたい。

研究成果

(24件)

すべてその他

すべて文献書誌 (24件)

[文献書誌] Yamazawa,T.: "A region of the ryanodine receptor critical for excitation-contraction coupling in skeletalmuscle." J.Biol.Chem.272. 8161-8164 (1997)
[文献書誌] Ikemoto,T.: "Functional and morphological features of skeletal muscle from mutant mice lacking both type 1 and type 3 ryanodine receptors." J.Physiol.501. 305-312 (1997)
[文献書誌] Kasai,Y.: "Endothelium-dependent frequency modulation of Ca^<2+> signaling in individual vascular smooth muscle cells of the rat." J.Physiol.504. 349-357 (1997)
[文献書誌] Takesako,K.: "Low-affinity fluorescent indicator for intracellular calciumions." Anal.Commun.34. 391-392 (1997)
[文献書誌] Hirose,K.: "Allosteric regulation by cytoplasmic Ca^<2+> and IP_3 of the gating of IP_3 receptors in guineapig vascular smooth muscle cells." J.Physiol.506. 407-414 (1998)
[文献書誌] Ito,K.: "Micromolar and submicromolar Ca^<2+> spikes regulating distinct cellular functions in pancreatic acinar cells." EMBOJ.16. 242-25110 (1997)
[文献書誌] Ninomiya,A.: " Kinetic diversity in the fusion of exocytotic vesicles.14" EMBOJ.16. 929-934 (1997)
[文献書誌] Takahashi,N.: "Multiple exocytotic pathways in pancreatic β-cells." J.CellBiol.138. 55-64 (1997)
[文献書誌] Sjoedin,L.: "Cytoplasmic Ca^<2+> gradients evoked by acetylcholine and peptides in Pancreatic acinar cells of the guinea pig." Pflugers Arch.433. 397-402 (1997)
[文献書誌] Mohri,T.: "Sperm-induced local [Ca^<2+>]_i rise separated from the Ca^<2+> wave in sea urchin eggs in the presence of a gamete fusion inhibitor,jaspisin." Development. (in press). (1998)
[文献書誌] Nakano,Y.: "Spatiotemporal dynamics of intracellular calcium in the mouse egg injected with a spermatozoon." Mol.Human Reprod.3. 1087-1093 (1997)
[文献書誌] Sato,Y.: "Adenophostin,a potent agonist of the inositol 1,4,5-trisphosphate receptor,is useful for fertilization of mouse eggs injected with round spermatids leading to normal offspring." Biol.Reprod.(in press). (1998)
[文献書誌] Kyozuka,K.: "Intracellular calcium oscillations and meiosis resumption from metaphase 1 induced by injection of the sperm extract in the acidian Ciona savignyi." Zool.Sci.(in press). (1998)
[文献書誌] Kamimoto,T.: "Dymple a novel dynamin-like high molecular weight GTPase lacking a proline-rich carboxyl-terminal domain in mammallian cells." J.Biol.Chem.273. 1044-1051 (1998)
[文献書誌] Muro,Y.: "Low frequency of autoantibies against Ki-67 antigen in Japanese patients with systemic autoimmune" J.Autoimm.10. 499-503 (1997)
[文献書誌] Nomoto,S.: "Functional analyses of mammalian protein kinase C isozymes in budding yeast and mammalian fibroblasts." Genes to Cells. 2. 601-614 (1997)
[文献書誌] Nagai,Y.: "Identification of a novel nuclear speckle-type protein,SPOP." FEBS lett.418. 23-26 (1997)
[文献書誌] Muro,Y.: "Autoantibody to thioredoxin reductase in an ovarian cancer patient." Biochem.Biophys.Res.Commun.(in press). (1997)
[文献書誌] Shimomura,A.: "Dominant negative ATF1 blocks cyclic AMP-induced neurite outgrowth in PC12D cells." J.Neurochem.(in press). (1997)
[文献書誌] Kuroyanagi,N,: "Novel SR-protein-specific kinase,SRPK2,disassembles nuclear speckles." Biochem,Biophys.Res.Commun.(in press). (1997)
[文献書誌] Masunaga,R.: "Alteration of platelet aggregation in patients with thyroid disorders." Metabolism. 46. 1128-1131 (1997)
[文献書誌] Watsuji,T.: "Controlled gene expression with a reverse tetracycline regulated retroviral vector(RTRV)system" Biochem.Biophys.Res.Commun.234. 769-773 (1997)
[文献書誌] Watanabe,Y.: "Characterization of a serum response factor-like protein in saccharomyces cerevisiae,Rlmi,which has transcriptional activity regulated by the Mpk1(Slt2)mitogen-activated protein kinase pathway." Mol.Cell.Biol.17. 2615-2623 (1997)
[文献書誌] Sugiura,K.: "Expression cloning and intracellular localization of a human ZF5 homologue." Biochem.Biophys.Acta.1352. 23-26 (1997)

1997 年度 実績報告書

細胞内情報伝達の生理機能解析と情報分子の可視化

研究代表者

飯野 正光 東京大学, 大学院・医学系研究科, 教授 (50133939)

研究成果

[文献書誌] Yamazawa,T.: "A region of the ryanodine receptor critical for excitation-contraction coupling in skeletalmuscle." J.Biol.Chem.272. 8161-8164 (1997)

[文献書誌] Ikemoto,T.: "Functional and morphological features of skeletal muscle from mutant mice lacking both type 1 and type 3 ryanodine receptors." J.Physiol.501. 305-312 (1997)

[文献書誌] Kasai,Y.: "Endothelium-dependent frequency modulation of Ca^<2+> signaling in individual vascular smooth muscle cells of the rat." J.Physiol.504. 349-357 (1997)

[文献書誌] Takesako,K.: "Low-affinity fluorescent indicator for intracellular calciumions." Anal.Commun.34. 391-392 (1997)

[文献書誌] Hirose,K.: "Allosteric regulation by cytoplasmic Ca^<2+> and IP_3 of the gating of IP_3 receptors in guineapig vascular smooth muscle cells." J.Physiol.506. 407-414 (1998)

[文献書誌] Ito,K.: "Micromolar and submicromolar Ca^<2+> spikes regulating distinct cellular functions in pancreatic acinar cells." EMBOJ.16. 242-25110 (1997)

[文献書誌] Ninomiya,A.: " Kinetic diversity in the fusion of exocytotic vesicles.14" EMBOJ.16. 929-934 (1997)

[文献書誌] Takahashi,N.: "Multiple exocytotic pathways in pancreatic β-cells." J.CellBiol.138. 55-64 (1997)

[文献書誌] Sjoedin,L.: "Cytoplasmic Ca^<2+> gradients evoked by acetylcholine and peptides in Pancreatic acinar cells of the guinea pig." Pflugers Arch.433. 397-402 (1997)

[文献書誌] Mohri,T.: "Sperm-induced local [Ca^<2+>]_i rise separated from the Ca^<2+> wave in sea urchin eggs in the presence of a gamete fusion inhibitor,jaspisin." Development. (in press). (1998)

[文献書誌] Nakano,Y.: "Spatiotemporal dynamics of intracellular calcium in the mouse egg injected with a spermatozoon." Mol.Human Reprod.3. 1087-1093 (1997)

[文献書誌] Sato,Y.: "Adenophostin,a potent agonist of the inositol 1,4,5-trisphosphate receptor,is useful for fertilization of mouse eggs injected with round spermatids leading to normal offspring." Biol.Reprod.(in press). (1998)

[文献書誌] Kyozuka,K.: "Intracellular calcium oscillations and meiosis resumption from metaphase 1 induced by injection of the sperm extract in the acidian Ciona savignyi." Zool.Sci.(in press). (1998)

[文献書誌] Kamimoto,T.: "Dymple a novel dynamin-like high molecular weight GTPase lacking a proline-rich carboxyl-terminal domain in mammallian cells." J.Biol.Chem.273. 1044-1051 (1998)

[文献書誌] Muro,Y.: "Low frequency of autoantibies against Ki-67 antigen in Japanese patients with systemic autoimmune" J.Autoimm.10. 499-503 (1997)

[文献書誌] Nomoto,S.: "Functional analyses of mammalian protein kinase C isozymes in budding yeast and mammalian fibroblasts." Genes to Cells. 2. 601-614 (1997)

[文献書誌] Nagai,Y.: "Identification of a novel nuclear speckle-type protein,SPOP." FEBS lett.418. 23-26 (1997)

[文献書誌] Muro,Y.: "Autoantibody to thioredoxin reductase in an ovarian cancer patient." Biochem.Biophys.Res.Commun.(in press). (1997)

[文献書誌] Shimomura,A.: "Dominant negative ATF1 blocks cyclic AMP-induced neurite outgrowth in PC12D cells." J.Neurochem.(in press). (1997)

[文献書誌] Kuroyanagi,N,: "Novel SR-protein-specific kinase,SRPK2,disassembles nuclear speckles." Biochem,Biophys.Res.Commun.(in press). (1997)

[文献書誌] Masunaga,R.: "Alteration of platelet aggregation in patients with thyroid disorders." Metabolism. 46. 1128-1131 (1997)

[文献書誌] Watsuji,T.: "Controlled gene expression with a reverse tetracycline regulated retroviral vector(RTRV)system" Biochem.Biophys.Res.Commun.234. 769-773 (1997)

[文献書誌] Watanabe,Y.: "Characterization of a serum response factor-like protein in saccharomyces cerevisiae,Rlmi,which has transcriptional activity regulated by the Mpk1(Slt2)mitogen-activated protein kinase pathway." Mol.Cell.Biol.17. 2615-2623 (1997)

[文献書誌] Sugiura,K.: "Expression cloning and intracellular localization of a human ZF5 homologue." Biochem.Biophys.Acta.1352. 23-26 (1997)

1997 年度実績報告書

飯野正光東京大学, 大学院・医学系研究科, 教授 (50133939)