Kalman D, Gomperts S N, Hardy S, Kitamura M, Bishop J M
Department of Microbiology and Immunology, G. W. Hooper Foundation Laboratories, University of California at San Francisco, San Francisco, California 94143, USA.
Mol Biol Cell. 1999 May;10(5):1665-83. doi: 10.1091/mbc.10.5.1665.
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.
在无神经元的培养物中，星形胶质细胞通常没有突起，尽管它们在体内有大量的突起。我们发现碱性成纤维细胞生长因子（bFGF）能诱导培养的星形胶质细胞长出突起，并且Ras家族GTP酶介导这些形态变化。当使用重组腺病毒将rac1和rhoA的激活等位基因导入解离培养的星形胶质细胞和脑片中时，它们阻断并逆转了bFGF的作用。相比之下，这两种GTP酶的显性负性（DN）等位基因模拟了bFGF的作用。Ha-ras的DN等位基因阻断了bFGF的作用，但没有阻断Rac1-DN或RhoA-DN的作用。我们的结果表明，通过c-Ha-Ras起作用的bFGF抑制内源性Rac1和RhoA GTP酶，从而触发星形胶质细胞突起生长，并且它们为体内尚未确定的神经元衍生因子对这一级联反应的调节提供了证据。
