| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Rho-family GTPases play key roles in regulating cytoskeletal reorganization, contributing to many aspects of nervous system development. Their activities are known to be regulated by guanine nucleotide exchange factors (GEFs), in response to various extracellular cues. We have been investigating several GEFs for Rac1, such as STEP, Tiam1 and P-Rex1. In this project, we have clarified that, in migrating neurons, STEP and Tiam1 activates Rac1-JNK pathway to phosphorylate MAP1B to regulate microtubule dynamics, eventually contributing to cortical neuronal migration. We have also shown that P-Rex1 transmits extra cellular signals, such as neurotrophins and EGF, to activate the Rac1 pathway, contributing to cortical neuronal migration. Furthermore, we have highlighted that Cdk5 phosphorylates and stabilizes p27kip1, which regulates RhoA-cofilin pathway, controlling actin cytoskeleton of processes of migrating neurons, contributing to cortical neuronal migration. These findings provide new insights into molecular machinery of neuronal network formation.
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