The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity

Nat Neurosci. 2004 Sep;7(9):923-9. doi: 10.1038/nn1295. Epub 2004 Aug 1.

Abstract

The establishment of a polarized morphology is an essential step in the differentiation of neurons with a single axon and multiple dendrites. In cultured rat hippocampal neurons, one of several initially indistinguishable neurites is selected to become the axon. Both phosphatidylinositol 3,4,5-trisphosphate and the evolutionarily conserved Par complex (comprising Par3, Par6 and an atypical PKC (aPKC) such as PKClambda or PKCzeta) are involved in axon specification. However, the initial signals that establish cellular asymmetry and the pathways that subsequently translate it into structural changes remain to be elucidated. Here we show that localization of the GTPase Rap1B to the tip of a single neurite is a decisive step in determining which neurite becomes the axon. Using GTPase mutants and RNA interference, we found that Rap1B is necessary and sufficient to initiate the development of axons upstream of Cdc42 and the Par complex.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal / metabolism
  • Axons / drug effects
  • Axons / metabolism
  • Body Patterning / drug effects
  • Body Patterning / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Cytochalasin D / pharmacology
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Embryo, Mammalian
  • GTP Phosphohydrolases / physiology
  • Gene Transfer Techniques
  • Green Fluorescent Proteins
  • Hippocampus / cytology
  • Immunohistochemistry / methods
  • Luminescent Proteins / metabolism
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Phalloidine / drug effects
  • Protein Kinase C / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • RNA Interference / physiology
  • RNA, Messenger / biosynthesis
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Time Factors
  • Transfection / methods
  • cdc42 GTP-Binding Protein / physiology*
  • rap GTP-Binding Proteins / physiology*
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Antibodies, Monoclonal
  • Carrier Proteins
  • Luminescent Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Pard3 protein, rat
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • tau-1 monoclonal antibody
  • Green Fluorescent Proteins
  • Phalloidine
  • Cytochalasin D
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • GTP Phosphohydrolases
  • Rap1b protein, mouse
  • Rap1b protein, rat
  • cdc42 GTP-Binding Protein
  • rap GTP-Binding Proteins
  • rhoA GTP-Binding Protein