Differential activation of Rac1 and RhoA in neuroblastoma cell fractions.
Differential activation of Rac1 and RhoA in neuroblastoma cell fractions.
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神经母细胞瘤细胞组分中 Rac1 和 RhoA 的差异激活。
DOI：
10.1016/j.neulet.2008.11.025
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发表时间：
2009
影响因子：
2.5
通讯作者：
Hynds,DiannaL
中科院分区：
文献类型：
--
作者：
Seifert,JenniferL;Som,Sonyta;Hynds,DiannaL
Rho鸟嘌呤核苷酸三磷酸酶（GTPases）Rac 1和RhoA是轴突生长的重要调节因子。然而，每一种都参与促进和抑制神经突生长，这使得每一种作用的具体作用变得复杂。Rac 1和RhoA在细胞体和生长锥中的激活的差异调节在指导轴突生长中可能是重要的。为了验证这一点，我们将神经母细胞瘤细胞分离成生长锥和细胞体部分，并评估Rac 1和RhoA对生长促进剂、血清戒断和8-溴腺苷-5 ′，3 ′-环磷酸（8-Br-cAMP）以及生长抑制剂、硫酸软骨素蛋白聚糖（CSPGs）或脑信号蛋白3A（Sema 3A）的激活。在全细胞裂解物中，血清提取减少，CSPGs或Sema 3A增加RhoA活性，但没有治疗影响Rac 1活性。在生长锥中，血清撤回或8-Br-cAMP增加Rac 1激活和血清撤回减少RhoA激活。相反，生长抑制剂降低Rac 1活性。此外，8-Br-cAMP逆转了由Sema 3A在全细胞裂解物中诱导的RhoA活性增加和生长锥中的CSPG。这些数据表明，RhoA和Rac 1的激活在特定的细胞区域受到不同的调节，这可能有助于Rho GTP酶介导的轴突生长的复杂性。
The Rho guanine nucleotide triphosphatases (GTPases) Rac1 and RhoA are important regulators of axon growth. However, the specific roles each plays are complicated by implications that each is involved in promoting and inhibiting neurite outgrowth. Differential regulation of Rac1 and RhoA activation in cell bodies and growth cones may be important in directing axon growth. To test this, we separated neuroblastoma cells into growth cone and cell body fractions and assessed Rac1 and RhoA activation in response to outgrowth promoters, serum withdrawal and 8-bromoadeosine-5′,3′-cyclic monophosphate (8-Br-cAMP), and outgrowth inhibitors, chondroitin sulfate proteoglycans (CSPGs) or semaphorin 3A (Sema 3A). In whole cell lysates, serum withdrawal decreased and CSPGs or Sema 3A increased RhoA activity, but no treatments affected Rac1 activity. In growth cones, serum withdrawal or 8-Br-cAMP increased Rac1 activation and serum withdrawal decreased RhoA activation. Conversely, outgrowth inhibitors decreased Rac1 activity. Additionally, 8-Br-cAMP reversed increases in RhoA activity induced by Sema 3A in whole cell lysates and CSPGs in growth cones. These data suggest that activation of RhoA and Rac1 is differentially regulated in specific cellular regions, perhaps contributing to the complexity of Rho GTPase-mediated axon growth.