The novel Rac effector RIN-1 regulates neuronal cell migration and axon pathfinding in C. elegans

Motomichi Doi, Hideki Minematsu, Yukihiko Kubota, Kiyoji Nishiwaki, Masaaki Miyamoto

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    Abstract

    Cell migration and axon guidance require proper regulation of the actin cytoskeleton in response to extracellular guidance cues. Rho/Rac small GTPases are essential regulators of actin remodeling. Caenorhabditis elegans CED-10 is a Rac1 homolog that is required for various cellular morphological changes and migration events and is under the control of several guidance signaling pathways. There is still considerable uncertainty regarding events following the activation of guidance receptors by extracellular signals and the regulation of actin dynamics based on spatiotemporally restricted Rac activity. Here we show that the VPS9 domain protein RIN-1 acts as a novel effector for CED-10 in C. elegans. The orthologous mammalian Rin1 protein has previously been identified as an effector for Ras GTPase and is now known to function as a guanine nucleotide exchange factor for Rab5 GTPase. 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 restricted neuronal cell types including AVM and HSN neurons, in contrast to the various defects observed in ced-10 mutants. Our analyses place RIN-1 in the Slit-Robo genetic pathway that regulates repulsive signaling for dorsoventral axon guidance. In rin-1 mutants, actin accumulated on both the ventral and dorsal sides of the developing HSN neuron, in contrast to its ventral accumulation in wild type. These results strongly suggest that RIN-1 acts as an effector for CED-10/Rac1 and regulates actin remodeling in response to restricted guidance cues.

    Original languageEnglish
    Pages (from-to)3435-3444
    Number of pages10
    JournalDevelopment (Cambridge)
    Volume140
    Issue number16
    DOIs
    Publication statusPublished - 2013 Aug 15

    Keywords

    • Actin remodeling
    • Axon pathfinding
    • Small GTpase

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology

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