| Budget Amount *help |
¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
Cell migration and axon guidance both require proper regulation of the actin cytoskeleton in response to extracellular guidance cues. Rho/Rac, a member of the small GTPase family, is an essential regulator of actin remodeling. Here we show that the VPS9-domain protein RIN-1 acts as a novel effector for CED-10 in C. elegans. We found that RIN-1 specifically binds to the GTP-bound form of CED-10, and that mutations in rin-1 cause significant defects in migration and axon guidance of some neuronal cell types. Our genetic analyses placed RIN-1 in the Slit-Robo genetic pathway that regulates repulsive signaling for dorso-ventral axon guidance. Furthermore, in rin-1 mutants, actin accumulated on both the ventral and dorsal sides of the developing HSN neuron. These results strongly suggest that RIN-1 acts as an effector for CED-10/Rac and regulates actin remodeling in response to restricted guidance cues.
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