Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway

Cell. 2001 Oct 19;107(2):195-207. doi: 10.1016/s0092-8674(01)00522-0.

Abstract

Mechanisms that regulate axon branch stability are largely unknown. Genome-wide analyses of Rho GTPase activating protein (RhoGAP) function in Drosophila using RNA interference identified p190 RhoGAP as essential for axon stability in mushroom body neurons, the olfactory learning and memory center. p190 inactivation leads to axon branch retraction, a phenotype mimicked by activation of GTPase RhoA and its effector kinase Drok and modulated by the level and phosphorylation of myosin regulatory light chain. Thus, there exists a retraction pathway from RhoA to myosin in maturing neurons, which is normally repressed by p190. Local regulation of p190 could control the structural plasticity of neurons. Indeed, genetic evidence supports negative regulation of p190 by integrin and Src, both implicated in neural plasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Axons / metabolism*
  • Cluster Analysis
  • Cytoskeleton / metabolism
  • DNA-Binding Proteins
  • Drosophila
  • GTPase-Activating Proteins
  • Gene Deletion
  • Genome
  • Guanine Nucleotide Exchange Factors / physiology*
  • Immunohistochemistry
  • Integrins / metabolism
  • Learning
  • Memory
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Myosin Light Chains / metabolism
  • Nuclear Proteins / physiology*
  • Phenotype
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Bacterial / metabolism
  • Rats
  • Repressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transgenes
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Arhgap35 protein, mouse
  • Arhgap35 protein, rat
  • Arhgap5 protein, mouse
  • DNA-Binding Proteins
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Integrins
  • Myosin Light Chains
  • Nuclear Proteins
  • RNA I
  • RNA, Bacterial
  • Repressor Proteins
  • rhoA GTP-Binding Protein

Associated data

  • GENBANK/AF387518