title: Rho GTPases regulate axon growth through convergent and divergent signaling pathways.
abstract: Rho GTPases are essential regulators of cytoskeletal reorganization, but how they do so during neuronal morphogenesis in vivo is poorly understood. Here we show that the actin depolymerization factor cofilin is essential for axon growth in Drosophila neurons. Cofilin function in axon growth is inhibited by LIM kinase and activated by Slingshot phosphatase. Dephosphorylating cofilin appears to be the major function of Slingshot in regulating axon growth in vivo. Genetic data provide evidence that Rho or Rac/Cdc42, via effector kinases Rok or Pak, respectively, activate LIM kinase to inhibit axon growth. Importantly, Rac also activates a Pak-independent pathway that promotes axon growth, and different RacGEFs regulate these distinct pathways. These genetic analyses reveal convergent and divergent pathways from Rho GTPases to the cytoskeleton during axon growth in vivo and suggest that different developmental outcomes could be achieved by biases in pathway selection.
authors.affiliation: Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA. julian.ng@kcl.ac.uk
authors.forename: Julian
authors.initials: J
authors.lastname: Ng
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D054461:Lim Kinases; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology; D024521:Mushroom Bodies / Q000294:innervation; D009474:Neurons / Q000166:cytology; D010641:Phenotype; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D054460:rho-Associated Kinases
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D011108:Polymers; C097180:tsr protein, Drosophila; D011494:Protein Kinases; D054461:Lim Kinases; C099277:Pak protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D054460:rho-Associated Kinases; C448559:ssh protein, Drosophila; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases; C511153:Rho1 protein, Drosophila; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins