Molecular dissection of organization and dynamics of lipid domains in biomembranes
| Project/Area Number |
17390025
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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 |
Biological pharmacy
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| Research Institution | RIKEN |
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Principal Investigator |
KOBAYASHI Toshihide RIKEN, Lipid Biology Laboratory, 小林脂質生物学研究室, 主任研究員 (60162004)
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| Co-Investigator(Kenkyū-buntansha) |
SHOGOMORI Hidehiko RIKEN, Sphingolipid Functions Laboratory, スフィンゴ脂質機能研究チーム, 研究員 (80391986)
ISHITSUKA Reiko RIKEN, Lipid Biology Laboratory, 小林脂質生物学研究室, 研究員 (60342747)
MAKINO Asami RIKEN, Sphingolipid Functions Laboratory, スフィンゴ脂質機能研究チーム, リサーチアソシエイト (20373368)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2006: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2005: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | Biomembrane / Lipid bilayer / Lipid domain / Lipid probe / Lipid raft / Endocytosis / Endosome / Cholesterol / 後期エンドソーム / ビス(モノアシルグリセロ)リン酸 / リゾビスボスファチジン酸 / ガングリオシド / スフィンゴリピドーシス / 膜結合毒素 / 膜ドメイン / スフィンゴミエリン / GM1 / シグナル伝達 |
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| Research Abstract |
(1) Characterization of lipid probes
Lysenin is a pore-forming toxin that specifically binds sphingomyelin (SM). The binding of the toxin to the membrane is accompanied by the oligomerization of the protein, leading to pore formation. Although a previous study showed that SM/cholesterol liposomes were 10,000 times more effective than SM liposomes in inhibiting lysenin-induced hemolysis, the role of cholesterol is not precisely clarified. Our results indicate that both cholesterol and the SM/lysenin ratio control the amount of lysenin monomer via altering the state of protein oligomerization, thus affecting hemolysis.
Duramycin is a 19 amino acid tetracyclic lantibiotic closely related to cinnamycin, which is known to bind phosphatidyl-ethanolamine (PE). The lipid specificity of duramycin was not established. Our study indicates that both duramycin and cinnamycin exclusively bind to ethanolamine phospholipids in curvature-dependent manner.
(2) Regulation of endocytosis by cholesterol
Cellular cholesterol increases when cells reach confluency in Chinese hamster ovary (CHO) cells. We showed that the endocytic pathways of several fluorescent lipids were altered in cell confluency-dependent manner. The crucial role of cellular cholesterol in cell-confluency dependent endocytosis was suggested. Our results also suggest that cholesterol controls endocytic routes of a subset of membrane lipids through rab11.
(3) Regulation of cellular cholesterol homeostasis by endosome lipid domains
Using D-PDMP and ganglioside GM1, it is shown that the structure alteration of bis (monoacylglycero) phosphate (BMP)-rich late endosome lipid domain plays a crucial role in cellular cholesterol accumulation. We also employed anti-BMP monoclonal antibody to examine the role of BMP domain in cholesterol homeostasis in macrophages.
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Report
(3 results)
Research Products
(49 results)
