| Project/Area Number |
09670017
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 Medical University |
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Principal Investigator |
ARAKI Nobukazu Kagawa Medical University, Anatomy, Associate Professor, 医学部, 助教授 (10202748)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Tetsuya Kagawa Medical University, Anatomy, Instructor, 医学部, 助手 (40243753)
HATAE Tanenori Kagawa Medical University, Anatomy, Professor, 医学部, 教授 (40037388)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | endocytosis / macropinocytosis / phagocytosis / F-actin / actin-binding proteins / α-actinin / macrophages / molecular machinery / アクチン結合蛋白 / ミオシン / コフィリン |
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| Research Abstract |
Macrophages show active macropinocytosis and phagocytosis which are F-actin-dependent cell motilities to take up extracellular solute and particles such as bacteria, respectively. These cell motilities also require a variety of actin-binding proteins which regulate F-actin polymerization, depolymerization and rearrangement. In order to elucidate the molecular machinery of macropinocytosis and phagocytosis, we have surveyed the involvement of several actin-binding proteins in macropinocytosis and phagocytosis, and revealed functional contributions of some of them. In this study, we have identified a myosin-mediated contractile activity that closes phagocytic cups into intracellular phagosomes in macrophages. It was shown that only myosin lc localized on the distal margin of the phagocytic cup, although other classes of myosins also distributed around phagocytic cups and/or phagosomes.
Then, we developed a new application of the fluorescence ratio imaging technique to in situ demonstration of the functional relationship between two related molecules such as F-actin and an actin-binding protein. Using this ratio imaging technique, we revealed that actinin-4, a novel isoform of alpha-actinin, was preferentially localized in circular ruffles, early macropinosomes in macrophages. These findings suggest that F-actin-bundling by actinin-4 may be functionally associated with macropinosomes formation and maintenance.
Furthermore, we are now continuing studies on other F-actin-binding proteins such as cofilin and ERM proteins.
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