Ras family GTPases control growth of astrocyte processes

Mol Biol Cell. 1999 May;10(5):1665-83. doi: 10.1091/mbc.10.5.1665.

Abstract

Astrocytes in neuron-free cultures typically lack processes, although they are highly process-bearing in vivo. We show that basic fibroblast growth factor (bFGF) induces cultured astrocytes to grow processes and that Ras family GTPases mediate these morphological changes. Activated alleles of rac1 and rhoA blocked and reversed bFGF effects when introduced into astrocytes in dissociated culture and in brain slices using recombinant adenoviruses. By contrast, dominant negative (DN) alleles of both GTPases mimicked bFGF effects. A DN allele of Ha-ras blocked bFGF effects but not those of Rac1-DN or RhoA-DN. Our results show that bFGF acting through c-Ha-Ras inhibits endogenous Rac1 and RhoA GTPases thereby triggering astrocyte process growth, and they provide evidence for the regulation of this cascade in vivo by a yet undetermined neuron-derived factor.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cells, Cultured / metabolism
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Cytoskeleton / ultrastructure
  • Fibroblast Growth Factor 2 / pharmacology
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / drug effects
  • GTP-Binding Proteins / metabolism*
  • Hippocampus / cytology
  • Rats
  • Rats, Sprague-Dawley
  • rac GTP-Binding Proteins
  • ras Proteins / genetics
  • ras Proteins / metabolism*
  • rhoA GTP-Binding Protein

Substances

  • Actins
  • Fibroblast Growth Factor 2
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • rac GTP-Binding Proteins
  • ras Proteins
  • rhoA GTP-Binding Protein