Crossveinless-c, the Drosophila homolog of tumor suppressor DLC1, regulates directional elongation of dendritic branches via down-regulating Rho1 activity

Genes Cells. 2010 May;15(5):485-500. doi: 10.1111/j.1365-2443.2010.01399.x. Epub 2010 Apr 7.

Abstract

Diverse neuronal subtypes develop distinctive morphologies of dendritic arbors that receive synaptic or sensory inputs. Dendritic arbors of many subtypes take on a polarized shape, and one underlying mechanism is unidirectionally biased elongation of dendritic branches. As reported herein, we found that Drosophila Crossveinless-c (Cv-c) was a key regulator for such directional growth. In the cv-c mutant, two subclass of multidendritic sensory neurons examined formed dorsally directed branches; however, dendritic branches had difficulty in growing along the anterior-posterior (A-P) body axis. Cv-c belongs to the family of Rho GTPase-activating proteins (RhoGAPs) and is the homolog of human tumor suppressor DLC1. The RhoGAP activity of Cv-c was required cell-autonomously for the A-P-oriented growth, and Cv-c elevated the GTPase activity of Rho1 and Cdc42 in a cell-free assay. Our analysis of genetic interactions suggested that Rho1 was the target of Cv-c in vivo. All of our results suggest that Cv-c contributes to sprouting and subsequent growth of the A-P-oriented branches through negative regulation of Rho1. We discuss a role of Cv-c in dendritic growth in response to environmental cues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Body Patterning / physiology
  • Dendrites / metabolism*
  • Dendrites / ultrastructure*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster* / anatomy & histology
  • Drosophila melanogaster* / physiology
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Phenotype
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • DLC1 protein, human
  • Drosophila Proteins
  • GTPase-Activating Proteins
  • Rac1 protein, Drosophila
  • Recombinant Fusion Proteins
  • Tumor Suppressor Proteins
  • cv-c protein, Drosophila
  • Rho1 protein, Drosophila
  • rac GTP-Binding Proteins
  • rho GTP-Binding Proteins