2006 Fiscal Year Final Research Report Summary
Molecular machinery and signal transduction of phagocytosis and macropinocytosis
| Project/Area Number |
15390056
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Kagawa University |
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Principal Investigator |
ARAKI Nobukazu Kagawa University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (10202748)
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| Co-Investigator(Kenkyū-buntansha) |
HATAE Tanenori Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (40037388)
EGAMI Youhei Kagawa University, Faculty of Medicine, Assistant, 医学部, 助手 (80432780)
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| Project Period (FY) |
2003 – 2006
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| Keywords | phagocytosis / macropinocytosis / signal transduction / phosphoinositides / cytoskeleton / molecular mechanism / imaging / image analysis |
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| Research Abstract |
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.
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