Molecular dissection of organization and dynamics of membrane lipid domains

膜脂结构域组织和动力学的分子解剖

• 批准号: 14370753
• 负责人: KOBAYASHI Toshihide
• 金额: $ 8.96万
• 依托单位: RIKEN
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370753/
• 关键词: Sphingomyelin; Lipid raft; Cholesterol; Lipid probe; Membrane domain; Lipid-binding toxin; Endocytosis; Flip-flop; 膜結合性毒素; 糖脂質; MDCK細胞; 細胞極性; エンドソーム; 脂質ドメイン; リゾビスホスファチジン酸; ホスファチジルエタノールアミン; 膜融合

Whereas the bilayer organization of biomembranes can be reconstituted in artificial liposomes with a simple lipid composition, biological membranes contain thousands of different lipid species, whose cellular distribution is stringently controlled. This complex distribution of lipids suggests that the targeting of lipids is highly regulated and that cells require a complex lipid supramolecular organization within their membranes. Our aim is to understand the organization, assembly and function of specific lipids and lipid domains. For this purpose, we developed several lipid-specific probes and a new inhibitor of Sphingolipid biosynthesis. These tools, in conjunction with biochemical, biophysical and cell biological approaches are now starting to provide valuable information to understand lipid supramolecular organization. Application of our probes uncovered several aspects of cellular lipid organization. Major subjects performed during these three years are :1.Characterization of sphingomyelin-specific toxin, lysenin2.Studies on organization and dynamics of sphingomyelin3.Characterization of sulfamisterin (AB5366), a new inhibitor of serine palmitoyltransferase4.Studies on distribution and transport of cholesterol-rich membrane domains5.Cellular distribution of phosphatidylethanolamine in yeast

尽管可以在具有简单的脂质组成的人造脂质体中重构生物膜的双层组织，但生物膜包含数千种不同的脂质物种，其细胞分布受到严格控制。这种脂质的复杂分布表明，脂质的靶向受到高度调节，并且细胞在其膜内需要复杂的脂质超分子组织。我们的目的是了解特定脂质和脂质域的组织，组装和功能。为此，我们开发了几种脂质特异性探针和新的鞘脂生物合成抑制剂。这些工具与生化，生物物理和细胞生物学方法结合使用，现在开始提供有价值的信息，以了解脂质超分子组织。我们的探针的应用发现了细胞脂质组织的几个方面。在这三年中执行的主要受试者是：1。鞘氨质特异性毒素，溶裂蛋白的特异性特异性。鞘磷脂的组织和动态。酵母中的磷脂酰乙醇胺

项目成果

Spatial and functional heterogeneity of sphingolipid-rich membrane domains

• DOI: 10.1074/jbc.m502244200
• 发表时间: 2005-06-24
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kiyokawa, E;Baba, T;Kobayashi, T
• 通讯作者: Kobayashi, T

石塚 玲子: "ラフトの概念"生体の科学. 54. 260-265 (2003)

石冢玲子：“筏概念”生物科学。 54. 260-265 (2003)

Sphingomyelin detecting probe

鞘磷脂检测探针

• 发表时间: 2002

Local exposure of phosphatidylethanolamine on the yeast plasma membranes is implicated in cell polarity

酵母质膜上磷脂酰乙醇胺的局部暴露与细胞极性有关

• 发表时间: 2004
• 期刊: Genes Cells 9
• 作者: Ishitsuka R;Ichimaru N;Yamaji-Hasegawa A;Ishitsuka R.;Kiyokawa E;Iwamoto K
• 通讯作者: Iwamoto K

Distribution and transport of cholesterol-rich membrane domains monitored by a membrane-impermeant fluorescent polyethylene glycol-derivatized cholesterol

• DOI: 10.1074/jbc.m313568200
• 发表时间: 2004-05-28
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Sato, SB;Ishii, K;Kobayashi, T
• 通讯作者: Kobayashi, T