| Project/Area Number |
14360053
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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 |
応用微生物学・応用生物化学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
UEDA Kazumitsu KYOTO UNIVERSITY Grad.Sch.Agric.Div.Appl.Life Sci, Professor, 農学研究科, 教授 (10151789)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Micliinori KYOTO UNIVERSITY Grad.Sch.Agric.Div.Appl.Life Sci, Assistant professor, 農学研究科, 助手 (00335308)
KIOKA Noriyuki KYOTO UNIVERSITY Grad.Sch.Agric.Div.Appl.Life Sci, Associate professor, 農学研究科, 助教授 (90234179)
天知 輝夫 京都大学, 農学研究科, 教授 (30301245)
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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 |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2003: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2002: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | ABC proteins / cholesterol / atherosclerosis / α1-syntrophin / lipid / HDL / transporter / membrane / 生活習慣病 / リン脂質 / 構造解析 |
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| Research Abstract |
This study was done to understand the molecular mechanism of ATP-dependent transporters involved in cholesterol and lipid homeostasis. ABCA1 mediates release of cellular cholesterol and phospholipid to form high density lipoprotein (HDL). ~The three different mutants in the first extracellular domain of human ABCA1 associated with Tangier disease, R587W, W590S, and Q597R, were examined for their subcellular localization and function by using ABCA1-GFP fusion protein stably expressed in HEK293 cells. Our study suggested that the defect of HILL assembly in R587W and Q597R is due to the impaired localization to PM, while W590S have functional defect other than the initial ATP binding and hydrolysis. Functions of ABCA1 are highly regulated at he transcriptional and post-transcriptional levels, and the synthesized ABCA1 protein turns over rapidly with a half-life of 1-2 hours. To examine if functions of ABCA1 are modulated by associated proteins, a yeast two-hybrid library was screened with the C-terminal 120 amino acids of ABCA1. Two PDZ proteins, α1-syntroplun and Lin7, were found to interact with ABCA1. Our -study suggested that α1-syntrophin is involved in intracellular signaling, which determines the stability of ABCA1, and modulates cellular cholesterol release.
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