| Project/Area Number |
12307003
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKENAWA Tadaomi Institute of Medical Science, Professor, 医科学研究所, 教授 (40101315)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Toshiki Institute of Medical Science, Associate Professor, 医科学研究所, 助手 (30313092)
FUKAMI Kiyoko Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (40181242)
三木 裕明 東京大学, 医科学研究所, 助手 (80302602)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥40,620,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥4,620,000)
Fiscal Year 2002: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2001: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2000: ¥20,600,000 (Direct Cost: ¥20,600,000)
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| Keywords | actin / cell movement / WASP / WAVE / cytoskeleton / 神経突起 / N-WASP / チロシンキナーゼ / ユビキチン化 |
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| Research Abstract |
It is already well known that a variety of cells rearrange cytoskeleton, prepare for cell division, and stimulate motility and migration in response to various stimuli. The directed migration of cells is one of fundamental phenomena of life, including migration toward inflammatory sites, and invasion and metastasis of cancer cells.
We found WASP and WAVE proteins which are related to cytoskeleton reorganization and cell migration. All these proteins have VCA regions at C-terminal area in which V region binds actin and CA region binds Arp2/3 complex. As a result, these proteins nucleate actin filaments and enhance actin polymerization. On the other hand, at N-terminal area, there are regions to which regulatory molecules bind. N-WASP binds several molecules such as WIP, WISH, Cdc42 and PIP2, and WAVE binds IRSp53, followed by the exposure of VCA region of these proteins. Consequently, these proteins bind to Arp2/3 complex and polymerize actin filaments. Finally, N-WASP which is located downstream of Cdc42 induces filopodia formation. WAVE which is located downstream of Rac induces lamellipodia formation. These proteins are present at the leading edge of moving cells and generate driving force.
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