| Project/Area Number |
12557001
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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 | 展開研究 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | NAGOYA UNIVERSITY |
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Principal Investigator |
FUJIMOTO Toyoshi NAGOYA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (50115929)
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| Co-Investigator(Kenkyū-buntansha) |
KOGO Hiroshi NAGOYA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 大学院・医学系研究科, 助手 (20282387)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | Caveolae / Calcium / Interstitial cells of Cajal / TRP4 / CAVEOLIN / Rab / 脂質滴 / ADRP / 低分子量GTP結合蛋白質 / 質量分析法 / コレステロール / シグナル伝達 / メサンギウム細胞 / MAPキナーゼ / カベオリン-1 / カベオリン-2 / 脂肪滴 |
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| Research Abstract |
Caveolae are plasmalemmal invaginations where receptors and signaling molecules are concentrated and may be important for signal transduction. We aimed to find out methods to regulate cellular functions by manipulating caveolae functions in living cells, and obtained the following results.
1) A transmembrane segment plus a short extracellular portion of a membrane protein were fused to caveolin molecules, to make artificial transmembrane proteins. One of the fusion proteins showed colocalization with endogenous caveolin-1, and by crosslinking an extracellular epitope by antibodies, it showed local aggregation. This method may be used to manipulate caveolae distribution from the extracellular surface.
2) By using interstitial cells of Cajal, we revealed that dihydropyridine-nonsensitive calcium oscillation is related to the pacemaker function, and that calcium influx through TRP4 in caveolae is involved in the oscillation. Caveolae also contains IP3 receptor and calcium pump, and thus TRP4 might be a target molecule for caveolae manipulation.
3) Lipid droplets contain a large amount of cholesterol as ester, and could harbor caveolins under some circumstances. We found a Rab protein (LD-Rab) exists in lipid droplets. Overexpression of LD-Rab caused changes in the molecular composition of lipid droplets, and also induced structural changes. LD-Rab is likely to be involved in the intracellular cholesterol trafficking, and a change of its expression level may affect the membrane microdomain.
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