| Project/Area Number |
14380350
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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 |
Developmental biology
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| Research Institution | RIKEN (The Institute of Physical and Chemical Research) |
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Principal Investigator |
NISHIWAKI Kiyoji RIKEN, Laboratory for Cell Migration, Team Leader, 細胞移動研究チーム, チームリーダー (30342827)
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| Co-Investigator(Kenkyū-buntansha) |
KUBOTA Yukihiko RIKEN, Laboratory for Cell Migration, Researcher, 細胞移動研究チーム, 研究員 (70333325)
SUZUKI Norio RIKEN, Laboratory for Cell Migration, Researcher, 細胞移動研究チーム, 研究員
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2003: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2002: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | cell migration / ADAM family / C.elegans / mutant / COG complex / C.elegans / コンドロイチン / ADAMfamily |
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| Research Abstract |
The secreted ADAM protease MIG-17 plays essential roles in regulation of directed migration of the distal tip cells (DTCs) that lead morphogenesis of the C.elegans gonad. MIG-17 is secreted from the body wall muscle cells and localized to the gonadal basement membrane to control DTC migration. The DTCs migrate in meandering or wandering mannerin the mig-17 mutants. To understand the molecular mechanisms involving MIG-17, we isolated and analyzed mutations having DTC migration abnormalities similar to those in the mig-17 mutants.
MIG-23 is an NDPase found in the Golgi apparatus and is required for glycosylation of proteins. We found that the glycosylation of MIG-17 is abnormal and that MIG17 failed to localize to the gonad in mig-23 mutants. We also found that MIG-23 affects DTC migration through the activity of MIG-17. Our findings indicate that mutations in an NDPase that is required for glycosylation of broad range of proteins can result in specific defects in organogenesis through disfunction of an ADAM protein. This work has been published in Nature Cell Biology. mig-29 and mig-30were found to encode homologous proteins of Cog3 and Cog1 that are required for vesicle trafficking in protein secretion. These are two of the eight components of the COG complex found in mammals. RNAi knock down of the remaining six homologes also caused DTC migration abnormality. These results shed new light on the COG vesicle trafficking complex in its function in cell migration.
In this project, we also succeeded in molecular cloning of mig-22 mig-26 and mig-24 mutations.
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