2007 Fiscal Year Final Research Report Summary
Molecular mechanism underlying cell polarity and cell migration
| Project/Area Number |
15GS0319
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| Research Category |
Grant-in-Aid for Creative Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Institution | Nagoya University |
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Principal Investigator |
KAIBUCHI Kozo Nagoya University, Graduate School of Medicine, Professor (00169377)
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| Co-Investigator(Kenkyū-buntansha) |
USUKURA Jiro Nagoya University, Center for Cooperative Research in Advanced Science&Technology, Professor (30143415)
KURODA Shinya University of Tokyo, Graduate School of Science, Professor (50273850)
AMANO Mutsuki Nagoya University, Graduate School of Medicine, Associate Professor (90304170)
TAYA Shinichiro Nagoya University, Graduate School of Medicine, Associate Professor (60362232)
ARIMURA Nariko Tamagawa University, Brain Science Institute, COE Associate Professor (20420375)
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| Project Period (FY) |
2003 – 2007
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| Keywords | polarily / axon / migration / CRMP-2 / Rho family / signal transduction / simulation / contraction |
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| Research Abstract |
Cell polarization is an essential step for cellular functions, but the underlying mechanisms to establish and maintain cell polarity are not fully understood. We tried to clarify the signal transduction mechanisms controlling cell polarization by the use of cell migration and neuronal axon/dendrite determination as model systems.
1. Identification of extracellular signals modulating neuronal polarity and following signaling pathways.
Extracellular signals such as laminin induced the production of PIP3, inactivation of GSK-3β, and resultant activation of CRMP-2. Active CRMP-2 bound to tubulin, Sra-1, and Numb, and regulated tubulin polymerization, actin remodeling, and L1 endocytosis at growth cone, which contributed to the axon elongation and neuronal axon/dendrite determination. In addition, Par complex composed of Par-3, Pare and aPKC modulated the Rac activity through Rac GEF (Tiam1/Tiam2) to establish neuronal polarity and front-rear polarity of migrating cells.
2. Analysis of signali
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ng pathways underlying cell migration
During establishment and maintenance of front-rear polarity in cell migration, Rac/IAGAP1 regulated dynamics of both actin and microtubules through APC/CLIP-170. Rho/Rho-kinase inhibited Par complex formation and adjusted the Rac activity properly both at the front and rear.
3. Role of molecular and vesicular traffic in cell polarization and migration
CRMP-2 interacted with tubulin, Sra-1 and Slp1/TrkB, and transported them to the tip of axon as a “cargo receptor". Numb regulated integrin endocytosis at the front of migrating cell, which is supposed to be necessary for directional migration.
4. Analysis of signal networks by computer simulation
The computational model for endothelial cell contraction (activation of myosin) suggested the existence of unidentified pathway for sustained cell contraction in silico, and the novel pathway mediated by iPLA2 was identified in vivo. The computational model for establishment of front-rear polarity of migrating cells by Rho family GTPases was developed. Less
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Research Products
(39 results)
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[Book] 細胞骨格と接着2006
Author(s)
貝淵弘三, 稲垣昌樹, 佐邊壽孝, 松崎文雄編
Total Pages
323
Publisher
共立出版
Description
「研究成果報告書概要(和文)」より
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