Ras family GTPases control growth of astrocyte processes
Ras family GTPases control growth of astrocyte processes
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DOI：
10.1091/mbc.10.5.1665
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发表时间：
1999-05-01
影响因子：
3.3
通讯作者：
Bishop, JM
中科院分区：
文献类型：
--
作者：
Kalman, D;Gomperts, SN;Bishop, JM
无神经元培养物中的星形胶质细胞通常缺乏突起，尽管它们在体内具有高度的突起。我们发现，碱性成纤维细胞生长因子（bFGF）诱导培养的星形胶质细胞生长过程和Ras家族GTP酶介导这些形态学变化。激活等位基因的rac 1和rhoA阻断和逆转bFGF的作用时，引入星形胶质细胞分离培养和脑切片中使用重组腺病毒。相比之下，显性阴性（DN）等位基因的两个GTP酶模仿bFGF的影响。Ha-uas的DN等位基因阻断bFGF的作用，但不阻断Rac 1-DN或RhoA-DN的作用。我们的研究结果表明，bFGF通过c-Ha-Ras抑制内源性的Rad和RhoA GTP酶，从而触发星形胶质细胞的过程中的增长，他们提供的证据，在体内调节这一级联反应的一个尚未确定的神经源性因子。
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-uas blocked bFGF effects but not those of Rac1-DN or RhoA-DN. Our results show that bFGF acting through c-Ha-Ras inhibits endogenous Rad 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.