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Molecular mechanisms underlying inhibition of full-length protein expression by interaction, with truncated protein of Cav channel

Research Project

Project/Area Number 14370017
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionOkazaki National Research Institute

Principal Investigator

OKAMURA Yasushi  Okazaki National Research Institute, Center for Integrative Bioscience, Professor, 統合バイオサイエンスセンター, 教授 (80201987)

Co-Investigator(Kenkyū-buntansha) 海老原 達彦  産業技術総合研究所, 脳神経情報研究部門, 研究員 (00344119)
IWASAKI Hirohide  Okazaki National Research Institute, National Institutes of Advanced Industrial Sciences and Technologies, Junior Researcher, 生理学研究所, 助手 (30342752)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2002: ¥5,900,000 (Direct Cost: ¥5,900,000)
Keywordsion channel / calcium / voltage-gated channel
Research Abstract

Truncated calcium channel subunits have been reported in developing tissue or in human channelopaties. However, functional significance of such truncated versions of proteins remain unknown. We studied molecular mechanisms underlying inhibition of expression of full length proteins by truncated proteins in Xenopus oocyte and BHK-G cells. Two electrode voltage clamp and whole cell patch clamp methods were applied on those cells. When truncated mammalian Cav1.2 subunit was coexpressed with the full length cDNA, remarkable suppression of channel expression was observed. This effect occurred at protein level, since introduction of premature stop codon eliminated this suppression. By Western blot analysis, it was shown that truncated protein is transferred into insoluble membrane fraction. Interestingly, the full length protein was also transferred to this fraction on coexpression with the truncated protein, indicating that misfolding of the truncated protein integrates the full length protein via unknown interactions and degradation or suppression of protein synthesis occurs. We also found that some truncated forms of voltage gated sodium channels show dominant-negative effects, suggesting that inhibitory mechanisms of truncated proteins are conserved among 4-motif type voltage gated channels.

Report

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

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Nakajo, K. et al.: "Development of transient outward currents coupled with Ca^<2+>-induced Ca^<2+> release mediates oscillatory membrane potential in ascidian muscle cell."Journal of Neurophysiology. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Izumi-Nakaseko, H. et al.: "DHP-insensitive L-type-like Ca channel of ascidian acquires sensitivity to DHP with single amino acid change is domain III P-reigon."FEBS letters. 549. 67-71 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Meinertzhagen, I. et al.: "The neurobiology of the ascidian tadpole larva : recent developments in an ancient chordate."Annual Rev.Neurosci.. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamura, Y. et al.: "The ascidian dihydropyridine-resistant calcium channel as the prototype of chordate L-type calcium channel"NeuroSignals. 12. 142-158 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ebihara, T. et al.: "Coexpression of a Cav1.2 protein lacking an N-ternimus and the first domain specifically suppresses L-type calcium channel activity."FEBS letters. 529. 203-207 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajo, K. et al.: "Identification, functional characterization and developmental expression of the ascidian Kv4-class potassium channel."Neurosci.Res.. 45. 59-70 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajo, K., Okamura, Y.: "Development of transient outward currents coupled with Cat-induced Ca^<2+> release mediates oscillatory membrane potential in ascidian muscle."J Neurophysiol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Izumi-Nakaseko, H., Yamaguchi, S., Ohtsuka, Y., Ebihara, T., Adachi-Akahane, S., Okamura, Y.: "DHP-insensitive L-type-like Ca channel of ascidian acquires sensitivity to DHP with single amino acid change in domain III P-region."FEBS letters. 549. 67-71 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamura, Y., Izumi-Nakaseko, H., Nakajo, K., Ohtsuka, Y., Ebihara, T.: "The ascidian dihydropyridine-resistant calcium channel as the prototype of chordite L-type calcium channel."Neurosignals. 12(3). 142-158 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajo, K., Katsuyama, Y., Ono, F., Ohtsuka, Y., Okamura, Y.: "Identification, functional characterization and developmental expression of the ascidian Kv4-class potassium channel."Neurosci.Res.. 45. 59-70 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ebihara, T., Komiya, Y., Izumi-Nakaseko, H., Adachi-Akahane, S., Okabe, S., Okamura, Y.: "Coexpression ofa Cav1.2 protein lacking an N-terminus and the first domain specifically suppresses L-type calcium channel activity."FEBS Lett.. 529. 203 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakajo, K. et al.: "Development of transient outward currents coupled with Ca2+-induced Ca2+ release mediates oscillatory membrane potential in ascidian muscle cell"Journal of Neurophysiology. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Izumi-Nakaseko, H. et al.: "DHP-insensitive L-type-like Ca channel of ascidian acquires sensitivity to DHP with single amino acid change in domain III P-region."FEBS letters. 549. 67-71 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Meinertzhagen, I. et al.: "The neurobiology of the ascidian tadpole larva : recent developments in an ancient chordate."Annual.Rev.Neurosci.. In press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Okamura, Y.et al.: "The ascidian dihyrdopyridine-resistant calcium channel as the prototype of chordate L-type calcium channel"NeuroSignals. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Ebihara, T.et al.: "Coexpression ofa Cav1.2 protein lacking an N-terminus and the first domain specifically suppresses L-type calcium channel activity"FEBS letters. 529. 203-207 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakajo, K.et al.: "Identification, functional characterization and developmental expression of the ascidian Kv4-class potassium channel"Neurosci. Res.. 45. 59-70 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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