Ras family GTPases control growth of astrocyte processes.
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.
Kalman
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Department of Microbiology and Immunology, G. W. Hooper Foundation Laboratories, University of California at San Francisco, San Francisco, California 94143, USA. kalman@cgl.ucsf.edu
Gomperts
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Hardy
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Kitamura
M
M
Bishop
J M
JM
D000199:Actins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020744:rac GTP-Binding Proteins; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein
D000199:Actins; D016222:Fibroblast Growth Factor 2; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein