Differential Effects of the Rac GTPase on Purkinje Cell Axons and Dendritic Trunks and Spines

Nature. 1996 Feb 29;379(6568):837-40. doi: 10.1038/379837a0.

Abstract

Neurons contain distinct compartments including dendrites, dendritic spines, axons and synaptic terminals. The molecular mechanisms that generate and distinguish these compartments, although largely unknown, may involve the small GTPases Rac and Cdc42, which appear to regulate actin polymerization. Having shown that perturbations of Rac1 activity block the growth of axons but not dendrites of Drosophila neurons, we investigated whether this also applies to mammals by examining transgenic mice expressing constitutively active human Rac1 in Purkinje cells. We found that these mice were ataxic and had a reduction of Purkinje-cell axon terminals in the deep cerebellar nuclei, whereas the dendritic trees grew to normal height and branched extensively. Unexpectedly, the dendritic spines of Purkinje cells in developing and mature cerebella were much reduced in size but increased in number. These 'mini' spines often form supernumerary synapses. These differential effects of perturbing Rac1 activity indicate that there may be distinct mechanisms for the elaboration of axons, dendrites and dendritic spines.

Publication types

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

MeSH terms

  • Animals
  • Ataxia / genetics
  • Ataxia / metabolism
  • Ataxia / pathology
  • Axons / metabolism*
  • Axons / ultrastructure
  • Cell Division
  • Cerebellum / metabolism
  • Cerebellum / ultrastructure
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Mutagenesis
  • Patch-Clamp Techniques
  • Purkinje Cells / enzymology
  • Purkinje Cells / metabolism*
  • Purkinje Cells / ultrastructure
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Synaptic Membranes / metabolism
  • rac GTP-Binding Proteins

Substances

  • Recombinant Fusion Proteins
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • rac GTP-Binding Proteins