| Project/Area Number |
17570146
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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 |
Molecular biology
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| Research Institution | Yokohama City University |
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Principal Investigator |
HIRAI Syu-ichi Yokohama City Univ., Medical Science, Associate Professor, 医学研究科, 準教授 (80228759)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | molecular biology / brain / neurogenesis / cell migration / DLK / JNK / axon / MAPキナーゼ / 輸送 / 発生 |
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| Research Abstract |
C-Jun N-terminal kinase (JNK) is implicated in regulating the various cellular events during neural development that include differentiation, apoptosis and migration. MUK (also named DLK) is a MAP kinase kinase kinase (MAPKKK) enzyme that activates JNK via MAP kinase kinases (MAPKK) such as MKK7. The expression of MUK protein in the developing mouse embryo is almost totally specific for the neural tissues, including central, peripheral, and autonomic nervous systems. We took a genetic approach to test the significance of MUK in the development of mouse neural tissues. MUK gene disruption resulted in decreases in JNK activity and in phosphorylation of known JNK substrates in the embryonic brain. Under these conditions, axon growth and radial migration of neocortical pyramidal neurons were significantly impaired. These data suggest that MUK plays a significant role in the coordinated regulation of radial migration and axon projection by modulating JNK activity. To investigate the molecular mechanism underlying the MUK function, we focused on JIP1, a scaffold molecule for MUK-JNK pathway, which functions in intracellular trafficking driven by kinesin motor. Our preliminary data indicate that activation of JNK by MUK can modulate JIP-dependent intracellular trafficking. We are now confirming this result and trying to clarify a novel molecular systems regulating neural cell differentiation.
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