Regulation of cross-talk among small GTPases in cell migration and neuronal axon pathfinding

2014 Fiscal Year Final Research Report

• Project/Area Number: 24570226
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: DOI Motomichi 独立行政法人産業技術総合研究所, バイオメディカル研究部門, 研究グループ長 (50344213)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 細胞移動 / 低分子量Ｇタンパク質 / 軸索伸長 / 細胞骨格

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.

Free Research Field

分子神経科学