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Molecular Mechanism on the Block of Neurotransmitter Release with Inositol Polyphosphates

Research Project

Project/Area Number 07680844
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOsaka University

Principal Investigator

NIINOBE Michio  Osaka University, Institute for Protein Research, Associate Professor, 蛋白質研究所, 助教授 (80135748)

Co-Investigator(Kenkyū-buntansha) ARUGA Jun  The Institute of Physical and Chemical Research, Researcher, ライフサイエンス筑波研究センター, 研究員 (10232076)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsSynaptotagmin / Inositol Polyphosphate / Neurotransmitter Release / Endocytosis
Research Abstract

We previously demonstrated that the C2B domain of synaptotagmin is an inositol polyphosphates (IPs) binding site, and synaptic transmission in squid giant synapse is completely blocked by injection of IPs into the presynaptic terminal. From these results, we suggested that synaptotagmin is a functional molecule directly involved in the neurotransmitter release, and is a target molecule of IPs in the block of synaptic transmission. In 1995, in order to verify this idea, we investigated whether specific antibody to the C2B domain (this antibody inhibits binding of IP4 to the C2B domain) is able to release the block of neurotransmission by IPs using squid giant synapse. The result revealed that the block of synaptic transmission is completely released with coinjection of IPs and the antibody. Moreover, with high frequent stimulation after injection of the antibody, synaptic response rapidly reduced, and drastical reduction of synaptic vesicle was observed. These results strongly suggest that synaptotagmin is a target molecule in the block of neurotransmission with IPs, and is involved in both phenomenons of exocytosis and endocytosis. In 1996, we performed a similar study in cell level using the primary culture from mammalian cells, rat superior cervical ganglion neurons (electrophysiological approarch) and bovine adrenal chromaffin cells (catecholamine release). The results demonstrated that the same phenomenons were observed on the blocking effect by IPs and release of block by coinjection with the C2B antibody. These results strongly suggest that IPs are ubiquitous modulator of synaptotagmin over the species.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Niinobe,M: "Synaptotagmin is an inositol poly phosphate binding protein. Isolation and characterization as an Ins-1, 3, 4, 5-P4 binding protein." Biochem. Biophys. Res. Commun.205. 1036-1042 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuda, M: "Inositol-1, 3, 4, 5-Tetrakis phos phate binding to C2B domain of IP4BP/Synaptotagmin II." J. Biol. Chem.269. 29206-29211 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Llinas, R: "The inositol high-polyphosphate series blocks synaptic transmission by preventing vesicular fusion. -A squid giant Synapse study." Proc. Natl. Acad. Sci. USA. 91. 12990-12993 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuda, M: "Functional diversity of C2 domains of synaptotagmin family-Mutational analysis of inositol high polyphosphate binding domain." J. Biol. Chem. 270. 26523-26527 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mikoshiba, K: "Role of the C2A domain of synaptotagmin in transmitlen release as determined by specific antibody injection into the squid giant symapse pretermind." Proc. Natl. Acad. Sci. USA. 92. 10703-10707 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuda, M: "Role of the C2B domain of synaptotagmin in vesicular release and recycling as determined by specific antiBody in jection into the squid giant synapse pretermind." Proc. Natl. Acad. Sci. USA. 92. 10708-10712 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamaguchi, Y: "Myelin proteolipid protein (PLP),but not DM-20, is an inosito hexalcis phosphate-binding protein." J. Biol. Chem.271. 27838-27846 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohara-Imaizumi, M: "Distinct roles of C2A and C2B domains of synaptotagmin in the requlation of exocytosis in adrenal chromaffin cells." Proc. Natl. Acad. Sci. USA. 94. 287-291 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mochida, S: "Roles of synaptotagmin C2 domains in neurotransmiffen secretion and inositol high-polyphos phate binding at mammalian cholinergic synapses." Neuroscience. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Niinobe, M.: "Synaptotagmin is an inositol polyphosphate binding protein. -Isolation and characterization as an Ins-1,3,4,5-P4 binding protein." Biochem.Biophys.Res.Commun.205. 1036-1042 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuda, M.: "Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II." J.Biol.Chem.269. 29206-29211 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Llinas, R.: "The inositol high-polyphosphate series blocks synaptic transmission by preventing vesicular fusion. -A squid giant synapse study." Proc.Natl.Acad.Sci.USA. 91. 12990-12993 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuda, M.: "Functional diversity of C2 domains of synaptotagmin family. -Mutational analysis of inositol high polyphosphate binding domain." J.Biol.Chem.270. 26523-26527 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mikoshiba, K.: "Role of the C2A domain of synaptotagmin in transmitter release as determined by specific antibody injection into the squid giant synapse preterminal." Proc.Natl.Acad.Sci.USA. 92. 10703-10707 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukuda, M.: "Role of the C2B domain of synaptotagmin in vesicular release and recycling as determined by specific antibody injection into the squid giant synapse preterminal." Proc.Natl.Acad.Sci.USA. 92. 10708-10712 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamaguchi, Y.: "Myelin proteolipid protein (PLP), but not DM-20, is an inositol hexakisphosphate-binding protein." J.Biol.Chem.271. 27838-27846 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohara-Imaizumi, M.: "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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mochida, S.: "Roles of synaptotagmin C2 domains in neurotransmitter secretion and inositol high-polyphosphate binding at mammlian cholinergic synapses." Neuroscience. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Niinobe,M: "Synaptotagmin is an Inositol Polyphosphate Binding Protein : Isolation and Characterization as an Ins1,3,4,5-P4 Binding Protain" Biochem.Biophys.Res.Commun. 205. 1036-1042 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fukuda,M: "Inositol-1,3,4,5-tetrakisphosphate Binding to C2B Domain of IP_4 BP/ Synaptotagmin II" J.Biol.Chem.269. 29206-29211 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Llinas.R: "The Inusitol High-Polyphosphate Series Blocks Synaptic Transmision by Preventing Vesicular Fusion : A squid Giant Synapse Study" Proc.Natl.Acad.Sci.USA. 91. 12990-12993 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fukuda,M: "Functional Diversity of C2 Domains of Synaptotagmin Family-Mutational Analysis of Inositol High Polyphosphate Binding Domain" J.Biol,Chem. 270. 26523-26527 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mikoshiba,M: "Role of C2A Domain of Synaptotagmin in transmition Release as Determined by Specific Autibody Injection into the Squid Giant Synapse" Proc.Natl.Acad.Sci.USA. 92. 10703-10707 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fukuda,M: "Role of the C2B Domain of Synaptotagmin in Vesicular Release and Recycling as Determined by Specific Antibody Injection into the Squid Giant Synapse" Proc.Natl.Acad.Sci.USA. 92. 10708-10712 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamaguchi,Y: "Myelim Proteolipid Protein (PLP),but not DM-20,is an Inositol Hexakisphate-binding Protein" J.Biol.Chem. 271. 27838-27846 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohara-Imaizumi,M: "Distinct roles of C2A and C2B domains of Synaptotagmin in the Regulation of Exeaytosis in Adrenal Chromatfin cells" Proc.Natl.Acad.USA. 94. 287-291 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Niinobe,M: "Synaptotagmin is an Inositol Polyphosphate Binding Protein : Isolation and Characterization as an Ins 1,3,4,5-P_4 Binding Protein" Biochem.Biophys.Res.Commun.205. 1036-1042 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fukuda,M: "Inositol-1,3,4,5-tetrakisphosphate Binding to C2B Domain of IP_4BP./Synaptotagmin II" J.Biol.Chem.269. 29206-29211 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Llinas,R: "The Inositol High-polyphosphate Series Blocks Synaptic transmission by Preventing Vesicular Fusion : A Squid Giant Synapse Study" Proc.Natl.Acad.Sci.USA. 91. 12990-12993 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fukuda,M: "Functional Diversity of C2 Domains of Synaptotagmin Family-Mutational Analysis of Inositol High Polyphosphate Binding Domain" J.Biol.Chem.270. 26523-26527 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mikoshiba,K: "Role of the C2A Domain of Synaptotagmin in transmitter Release as Determined by Specific Antibody Injection into the Squid Giant Synapse" Proc.Natl.Acad.Sci.USA. 92. 10703-10707 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fukuda,M: "Role of the C2B Domain of Synaptotagmin in Vesiwlar Release and Recyding as Determined by Specific Antibody Injection into the Squid Giant Synapse" Proc.Natl.Acad.Sci.USA. 92. 10708-10712 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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