• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

MOLECULAR MECHANISMS OF TRANSMITTER RELEASE

Research Project

Project/Area Number 10044215
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionSOPHIA UNIVERSITY

Principal Investigator

KUMAKURA Konosuke  Sophia University, Faculty of Science and Technology, Professor, 理工学部, 教授 (70129790)

Co-Investigator(Kenkyū-buntansha) MOCHIDA Sumiko  Tokyo Medical College, Department of Pysiology, Associate Professor, 医学部, 助教授 (30096341)
KOZAKI Shunji  Osaka Prefecture University, College of Agriculture, Professor, 農学部, 教授 (10109895)
TAKAHASHI Masami  Mitsubishi Kasei Institute of Life Sciences, Project Center, Cheif, プロジェクトセンター, プロジェクトセンター長
IMAIZUMI Mica  Sophia University, Faculty of Science and Technology, Assistant, 理工学部, 助手 (40201941)
SASAKAWA Nobuyuki  Sophia University, Faculty of Science and Technology, Associate Professor, 理工学部, 助教授 (20187107)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1999: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1998: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsTransmitter Release / Chromaffin Cell / Synaptotagmin / Inositol Polyphosphate / C Kinase / F-actin / RACK1 / SNARE Proteins / F.アクチン
Research Abstract

The aim of this research project is to elucidate the molecular mechanism of neurotransmitter release in collaboration with French group. The studies focused on 1) the mechanism of vesicle recruitment and priming, 2) the mechanism of fusion of vesicles in response to Ca^<2+> signals, and we have obtained the following results.
1. The mechanism of vesicle recruitment and priming.
1) We have suggested that binding of inositol polyphosphates to C2 domain of synaptotagmin acts as an inhibitory clamp for the exocytosis. We clarified that the bound inositol polyphosphates dissociate from synaptotagmin in response to Ca^<2+> in chromaffin cells. Microinjected inositol hexakisphosphate inhibited both the evoked and spontaneous exocytosis, while inositol hexakissulfate failed to inhibit.
2) We clarified that the subplasmalemmal actin network and actin-myosin interaction are essential for the vesicle recruitment and priming. We also found that the facilitation of the priming by protein kinase C (PKC) is mediated through the complex between the activated PKC α or PKC β, their receptor molecule RACK1 and cortical F-actin.
2. The mechanism of fusion of vesicles in response to Ca^<2+> signals.
1) Studies with subclones of PC12 cells demonstrated that the reduced expression of syntaxin, VAMP-2, SNAP-25 and Munc-18 decreased the exocytotic activity.
2) Studies on synaptic transmission clarified the recycle of SNARE proteins and binding of SNARE proteins with N-type Ca^<2+>-channels. It was also found that binding of Doc2 α to Munc13-1 precedes exocytosis.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Hiroaki Misonou: "Protein Kinase C controls the priming step of regulated exocytosis in adronal chromaffin cells."Celluler and Molecular Neurobiology. 18(4). 379-390 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 今泉美佳: "イノシトールポリリン酸の役割;開口分泌における調節作用"蛋白質・核酸・酵素. 43(12). 1789-1793 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Konosuke Kumakura: "Inhibitory clamps of regulated exocytosis and role of Ca^<2+> ; clamp by synaptotagmin and inositol polyphosphates."The Adrenal Chromaffin Cell (eds.T.Kanno,Y.Nakazato,K.Kumakura). 199-211 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Konosuke Kumakura: "Roles of Synaptotagmin and Inositol Polyphosphates in the Mechanism of Exocytosis ; The Clamp Hypothesis."Keio University Symposia for Life Science and Medicine, Vol.2 Neural Development. 2. 450-455 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jeanne-Andree Boudier: "Redistribution of presynaptic proteins during α-latrotoxin-induced release of neurotransmitter and membrane retrieval at the frog neuromuscular junction."Eur.J.Neurosci.. 11. 3449-3456 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Makoto Itakura: "Transfection Analysis of Functional Roles of Complexin I and II in the Exocytosis of Two Different Type of Secretory Vesicles."Biochem.Biophys.Res.Commun.. 265. 691-696 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Michael Seagar: "Interactions between proteins implicated in exocytosis and voltage-gated calcium channels."Prie.Trans.R.Soc.Lond.B. 354. 289-297 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sumiko Mochida: "Role of the Doc2 α-Munc13-1 interaction in the neurotransmitter release process."Proc.Natl.Acad.Sci.USA. 95. 11418-11422 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sumiko Mochida: "Evidence for a voltage-dependent enhancement of neurotransmitter release mediated via the synaptic protein interaction site of N-type Ca^<2+> channels."Proc.Natl.Acad.Sci.USA. 95. 14523-14528 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jeffrey M.Ilardi: "A SNARE-associated protein implicated in synaptic transmission."Nature Neuroscience. 2. 119-214 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] G.Lao: "Syntaphilin : a synataxin-1 clamp that controls SNARE assembly."Neuron. 25. 191-201 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shunji Kozaki: "Ganglioside GT1b as a complementary receptor component for Clostridium botulinum neurotoxins."MICROBIAL PATHOGENESIS. 25. 91-99 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shunji Kozaki: "Characterization of Clostridium botulinum Type B Neurotoxin Associated with Infant Botulism in Japan."INFECTION AND IMMUNITY. 66. 4811-4816 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroaki Misonou: "Protein Kinase C controls the priming step of regulated exocytosis in adronal chromaffin cells."Celluler and Molecular Neurobiology. 18(4). 379-390 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mica Ohara-Imaizumi, Konosuke Kumakura: "Roles of Inositol Polyphosphates in The Regulation of Exocytosis."Protein, Nucleic Acid and Enzyme. 43(12). 1789-1793 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Konosuke Kumakura: "Inhibitory clamps of regulated exocytosis and role of Ca^<2+> ; clamp by synaptotagmin and inositol polyphosphates."The Adrenal Chromaffin Cell (eds.T.Kanno, Y.Nakazato, K.Kumakura). 199-211 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Konosuke Kumakura: "Roles of Synaptotagmin and Inositol Polyphosphates in the Mechanism of Exocytosis ; The Clamp Hypothesis."Keio University Symposla for Life Science and Medicine, Neural Development. Vol.2. 450-455 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jeanne-Andree Boudier: "Redistribution of presynaptic proteins during α-latrotoxin-Induced release of neurotransmitter and membrane retrieval at the frog neuromuscular junction."Eur.J.Neurosci.. 11. 3449-3456 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Makoto Itakura: "Transfection Analysis of Functional Roles of Complexin I and II in the Exocytosis of Two Different Types of Secretory Vesicles."Biochem.Biophys.Res.Commun.. 265. 691-696 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Michael Seagar: "Interactions between proteins implicated in exocytosis and voltage-gated calcium channels."Prie.Trans.R.Soc.Lond.B. 354. 289-297 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sumiko Mochida: "Role of the Doc2 α-Munc13-1 interaction in the neurotransmitter release process."Proc.Natl.Acad.Sci.USA. 95. 11418-11422 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sumiko Mochida: "Evidence for a voltage-dependent enhancement of neurotransmitter release mediated via the synaptic protein interaction site of N-type Ca^<2+> channels."Proc.Natl.Acad.Sci.USA. 95. 14523-14528 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jeffrey M.Ilardi: "A SNARE-associated protein implicated in synaptic transmission."Nature Neuroscience. 2. 119-214 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] G.Lao: "Syntaphilin : a synataxin-1 clamp that controls SNARE assembly."Neuron. 25. 191-201 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shunji Kozaki: "Ganglioside GT1b as a complementary receptor component for Clostridium botulinum neurotoxins."MICROBIAL PATHOGENESIS. 25. 91-99 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shunji Kozaki: "Characterization of Clostridium botulinum Type B Neurotoxin Associated with Infant Botulism in Japan."INFECTION AND IMMUNITY. 66. 4811-4816 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Konosuke Kumakura: "Roles of synaptotagmin and inositol polyphosphates in the mechanism of exocytosis;The Clamp Hypothesis."Keio University Symposia for Life Science and Medicine,Vol.2 Neural Development. 2. 450-455 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jeffrey M.Ilardi: "A SNARE-associated protein implicated in synaptic transmission."Nature Neuroscience. 2. 119-214 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] G.Lao: "Syntaphilin:a syntaxin-1 clamp that controls SNARE assembly."Neuron. 25. 191-201 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Boudier JA: "Redistribution of presynaptic proteins during alpha-latrotoxin-Induced release of neuro transmitter and membrane retrieval at the frog neuromuscular junction."Eur.j.Neurosci.. 11. 3449-3456 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Itakura M: "Trabsfection analysis of functional roles of complexin I and Il in the exocytosis of two different types of secretoty vesicles."Biochemi.. 265. 691-696 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Michael Seagar: "Interactions between proteins implicated in exocytosis and voltage-gated calcium channels."Prie.Trans.R.Soc.Lond.B. 354. 289-297 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroaki Misonou: "Protein Kinase C controls the priming step of regulated exocytosis in adronal chromaffin cells." Celluler and Molecular Neurobiology. 18(4). 379-390 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 今泉 美佳: "イノシトールポリリン酸の役割;開口分泌における調節作用" 蛋白質・核酸・酵素. 43(12). 1789-1793 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kounosuke Kumakura: "Inhibitory clamps of regulated exocytosis and role of Ca^<2+>;clamp by synaptotagmin and inositol polyphosphates." The Adrenal Chromaffin Cell(eds.T.Kanno,Y.Nakazato,K.Kumakura). 199-211 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kounosuke Kumakura: "Roles of synapto tagmin and inositol pholyphosphatea in the mechanism of exocytosis;The Clamp Hypothesis." Keio University Symposia for Life Science and Medicine,Vol.2 Neural Development. 450-455 (1999)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1998-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi