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Functional analyses of the mouse mitochondrial GTPase, mOPAI. -identification of binding proteins and subcellular localization -

Research Project

Project/Area Number 13470007
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KUBO Yoshihiro  Tokyo Medical and Dental University Graduate School, Department of Physiology, Professor, 大学院・歯学総合研究科, 教授 (80211887)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥8,200,000 (Direct Cost: ¥8,200,000)
Keywordslarge GTP binding protein / neuron / mitochondria / optic nerve atrophy / mutant / fragmentation / GTP結合蛋白質 / CDNA / dynamin / 細胞内局在
Research Abstract

It has been reported that mutations of one of the dynamin family GTPases OPA1 cause autosomal dominant optic atrophy, the most frequent form of hereditary optic neuropathies. Although the involvement of OPA1 abnormality in neurodegenerative disease is apparent, little is known about the cell biological and biochemical functions of OPA1. To approach the pathophysiological mechanism of autosomal dominant optic atrophy, we have analyzed the effects of overexpressed mouse OPA1 (mOPAI) on mitochondrial morphology in transfected COS-7 cells. By the overexpression of wild type mOPA1, mitochondria of transfected cells changed their shapes to a fragmented pattern. Accordingly, the intermembrane space was distributed unevenly in the fragmented and small ring shaped mitochondria, being concentrated at one end. We observed by immunoelectron microscopy of transfected cells that the membrane structures of mitochondria changed dramatically; the inner membranes were concentrated at one end. When transfected with mOPA1 mutants with loss of function mutation in the GTP-binding domain, fragmentation of mitochondria still occurred, but the impartial distribution of intermembrane space were observed no more. These results show that GTP-dependent reaction is involved in the dramatic change of the inner membrane. We also observed that the effect of some of missense mutations with autosomal dominant optic atrophy resembled to that of the negative mutation in G1 motif.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Misaka, T., Miyashita, T., Kubo, Y.: "Primary structure of adynosin-related mouse mitochondrial GTPase and its discributon in brain, subcelluar localization and effect on mitochondrial morophology"J.Biol.Chem. 277. 15834-15842 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saitoh, O., Murata, Y., Odagiri, M., Itoh, M., Itoh, H., MIsaka, T., Kubo, Y.: "Alternative splicing of RGS8 gene determines inhibitory function of receptor-type specific Gq signaling"Proc.Natl.Acad.Sci., USA. 99. 10138-10143 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe, H., Misaka, T., Tateyama, M., Kubo, Y.: "Effects of co-expression with Homer isoforms on the function of methohotropic glutamate receptor 1a."Molec.Cellul.Neurosci.. 23. 157-168 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe, H., Tateyama, M., Kubo, Y.: "Functional identification of Gd^<3+> binding site of metabotropic glutamate recetor 1a."FEBS lett.. 545. 233-238 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tateyama, M., Abe, H., Nakata, H., Saitoh, O., Kubo, Y.: "Ligand-induced rearrangement of the intracellular dimeric conformation of metabotropic glutamate receptor 1a."Nature Strncl.Molec.Biol.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Misaka, T., Miyashita, T., Kubo, Y.: "Primary structure of a dynamin-related mouse mitochondrial GTPase and its distribution in brain, subcellular localization and effect on mitochondrial morphology."Journal of Biological Chemistry. 277. 15834-15842 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saitoh, O., Murata, Y., Odagiri, M., Itoh, M., Itoh, H., Misaka, T., Kubo, Y.: "Alternative splicing of RGS8 gene determines inhibitory function of receptor-type-specific Gq signaling."Proc.Natl.Acad.Sci.USA. 99. 10138-10143 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe, H., Misaka, T., Tateyama, M., Kubo, Y.: "Effects of co-expression with Homer isoforms on the function of metabotropic glutamate receptor1a."Molecular and Cellular Neuroscience. 23. 157-168 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe, H., Tateyama, M., Kubo, Y.: "Functional identification of Gd^<3+> site of metabotropic glutamate receptor1a."FEBS letters. 545. 233-238 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tateyama, M., Abe, H., Nakata, H., Saitoh, O., Kubo, Y.: "Ligand-induced rearrangement of the intracellular dimeric conformation of metabotropic glutamate receptor1a."Nature Structural & Molecular Biology. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe, H., Misaka, T., Tateyama, M., Kubo, Y.: "Effect of co-expression with Homer isoforms on the function of metabotropic glutamate receptorla."Molecular and Cellular Neuroscience. 23. 157-168 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Abe, H., Tateyama, M., Kubo, Y.: "Functional identification of Gd3+ binding site of metabotropic glutamate receptorla."FEBS letters. 545. 233-238 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Saitoh, O., Kubo, Y.: "Biochemical and Physiological Properties of Regulator of G protein Signaling 8."Recent Res.Develop.Biopyhys.Biochem.. 3. 269-289 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Misaka, T., Miyashita, T., Kubo, Y.: "Primary Structure of a dynamin-related mouse mitochondrial GTPase and its distribution in brain subcullular locallization ane effect on mitochondorial morphology"Journal of Biological Chemistry. 277. 15834-15842 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ai, T., Fujiwara, Y., Tsuji, K., Otani, H., Nakano, S., Kubo, Y., Horie, M.: "Noel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia"Circulation. 105. 2592-2594 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saitoh, O., Murata, Y., Odagiri, M., Itoh, H., Misaka, T., Kubo, Y.: "Alternative splicing of RGS8 gene determines inhibitory function of receptor-type-spencific G9 signaling"Proceedings of National Academy of Sciences USA. 99. 10138-10143 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murata, Y., Fujiwara, Y., Kubo, Y.: "Identification of a site involved in the block by extracellular Mg^<2+> and Ma^<2+> aswell as permeation of K^+Kir2.1K^+ channel"Journal of Physiology. 544. 665-677 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujiwara, Y., Kubo, Y.: "Ser 165 in the second transmembrane region of the Kir2.1 channel determines its susceptibility to blocked by intracellular Mg^<2+>"Journal of General Physiology. 120. 677-692 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Abe, H., Misaka, T., Tateyama, M., Kubo, Y.: "Effects of co-expression with Homer isoforums on the function of metabotropic glutamate receptor1α"Molecular and Cellular Neuroscience. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kubo Y, Murata Y.: "Control of rectification and permeation by two distinct sites after the second transmembrane region in Kir2.1 K^+ channel"J Physiol. 531. 645-660 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saitoh O, Masuho I, Terakawa I, Nomoto S, Asano T, Kubo Y.: "RGS8 requires its N-terminus for subcellular localization and acute desensitization of G protein gated K^+ channels"J Biol Chem. 276. 5052-5058 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Murata Y, Okado H, Kubo Y.: "Characterization of heteromultimeric G-protein coupled inwardly rectifying potassium channels of the tunicate tadpole with a unique property"J Biol Chem. 276. 18529-18539 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Murata Y, Okado H, Katsuyama Y, Okamura Y, Kubo Y: "Primary Structure developmental expression and functional properties of an inward rectifier K^+ channel of tunicate"Receptors and Channels. 7. 387-399 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Soom M, Schonherr R, Kubo Y, Kirsch C, Klinger R, Heinemann SH.: "Multiple PIP_2 binding sites in Kir2.1 inwardly rectifying potassium channels"FEBS lett. 490. 49-53 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Misaka T, Miyashita T, Kubo Y.: "Primary structure of a dynamin-related mouse mitochondrial GTPase and its distribution in brain, subcellular localization and effect on mitochondrial morphology"J Biol Chem. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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