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

尽管生物膜的双层组织可以用简单的脂质组成在人工脂质体中重构，但生物膜含有数千种不同的脂质物质，其细胞分布受到严格控制。脂质的这种复杂分布表明脂质的靶向是高度调节的，并且细胞在其膜内需要复杂的脂质超分子组织。我们的目标是了解特定脂质和脂质结构域的组织，组装和功能。为此，我们开发了几种脂质特异性探针和一种新的鞘脂生物合成抑制剂。这些工具，结合生物化学，生物物理和细胞生物学方法，现在开始提供有价值的信息，了解脂质超分子组织。我们的探针的应用揭示了细胞脂质组织的几个方面。主要研究内容有：1.鞘磷脂特异性毒素Lysenin的特性2.鞘磷脂的结构和动力学研究3.丝氨酸棕榈酰转移酶抑制剂磺胺酯（AB 5366）的特性4.富含胆固醇的膜结构域的分布和转运研究5.磷脂酰乙醇胺在酵母细胞中的分布

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

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

Sphingomyelin detecting probe

鞘磷脂检测探针

• 发表时间: 2002

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)

Recognition of sphingomyelin by lysenin and lysenin-related proteins

• DOI: 10.1021/bi049561j
• 发表时间: 2004-08-03
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Kiyokawa, E;Makino, A;Kobayashi, T
• 通讯作者: Kobayashi, T