| Project/Area Number |
14370017
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Okazaki National Research Institute |
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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)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| 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)
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| Keywords | ion channel / calcium / voltage-gated channel |
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| 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.
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