Molecular machinery and signal transduction of phagocytosis and macropinocytosis

吞噬作用和巨胞饮作用的分子机制和信号转导

基本信息

批准号：
15390056
负责人：
ARAKI Nobukazu
金额：
$ 9.47万
依托单位：
Kagawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

Phagocytosis and macropinocytosis are endocytic cell surface movements for taking extracellular particles such and fluid, respectively, and play important roles in innate immunity and antigen presentation. These cell surface movements are mediated by molecular machineries driving F-actin reorganization and membrane traffic, which are ingeniously controlled by complicated signal transduction pathways. The main aim of this research project is to resolve the relationship between molecular machineries and phosphoinositide signal during phagocytosis and macropinocytosis.In this study using bioimaging and image analysis, we revealed that levels of PI(4,5)P2 and PI(3,4,5)P3 in the membrane of forming macropinosomes were closely linked to the changes in actin cytoskeleton. The concentrations of PI(4,5)P2 in the membrane ruffles forming macropinocytic cups increased more than double that in other areas. The PI(4,5)P2 levels reached its maximum just before closing into macropinosomes, and rapidly fell after macropinosome internalization. In contrast, the PI(3,4,5)P3 was locally produced at the site of macropionosome formation around the time of macropinosome internalization. Our findings suggest that locally controlled levels of phosphoinositides by class I PI3kinase are important for regulating the function of actin-binding proteins which affect changes in the cell surface membrane architecture. Furthermore, we have shown that PI(3)P which is the main product of class III PI3kinase is essential for the fusion of formed macropinosomes.

吞噬作用和大细胞增多症是内吞细胞表面运动，分别用于服用细胞外颗粒和液体，并在先天免疫和抗原表现中起重要作用。这些细胞表面运动是由驱动F-肌动蛋白重组和膜流量的分子机制介导的，这些机械由复杂的信号转导途径巧妙地控制。 The main aim of this research project is to resolve the relationship between molecular machineries and phosphoinositide signal during phagocytosis and macropinocytosis.In this study using bioimaging and image analysis, we revealed that levels of PI(4,5)P2 and PI(3,4,5)P3 in the membrane of forming macropinosomes were closely linked to the changes in actin cytoskeleton.在膜荷叶边形成大型细胞杯的PI（4,5）P2的浓度在其他地区增加了两倍以上。 PI（4,5）P2水平在接近大型体体之前达到了最大值，并在大型内部化后迅速下降。相比之下，PI（3,4,5）P3是在大型肌体内部化时期在大焦点形成部位局部生产的。我们的发现表明，I类PI3Kinase的局部控制水平的磷酸肌醇水平对于调节影响细胞表面膜结构变化的肌动蛋白结合蛋白的功能很重要。此外，我们已经表明，这是III类PI3Kinase的主要产物Pi（3）P对于形成的大型大体的融合至关重要。