| First Author | Iwasawa N | Year | 2012 |
| Journal | Mol Biol Cell | Volume | 23 |
| Issue | 14 | Pages | 2793-804 |
| PubMed ID | 22593211 | Mgi Jnum | J:198767 |
| Mgi Id | MGI:5499092 | Doi | 10.1091/mbc.E12-02-0103 |
| Citation | Iwasawa N, et al. (2012) R-Ras controls axon branching through afadin in cortical neurons. Mol Biol Cell 23(14):2793-804 |
| abstractText | Regulation of axon growth, guidance, and branching is essential for constructing a correct neuronal network. R-Ras, a Ras-family small GTPase, has essential roles in axon formation and guidance. During axon formation, R-Ras activates a series of phosphatidylinositol 3-kinase signaling, inducing activation of a microtubule-assembly promoter-collapsin response mediator protein-2. However, signaling molecules linking R-Ras to actin cytoskeleton-regulating axonal morphology remain obscure. Here we identify afadin, an actin-binding protein harboring Ras association (RA) domains, as an effector of R-Ras inducing axon branching through F-actin reorganization. We observe endogenous interaction of afadin with R-Ras in cortical neurons during the stage of axonal development. Ectopic expression of afadin increases axon branch number, and the RA domains and the carboxyl-terminal F-actin binding domain are required for this action. RNA interference knockdown experiments reveal that knockdown of endogenous afadin suppressed both basal and R-Ras-mediated axon branching in cultured cortical neurons. Subcellular localization analysis shows that active R-Ras-induced translocation of afadin and its RA domains is responsible for afadin localizing to the membrane and inducing neurite development in Neuro2a cells. Overall, our findings demonstrate a novel signaling pathway downstream of R-Ras that controls axon branching. |
