Overexpression of a neural-specific Rho family GTPase, cRac1B, selectively induces enhanced neuritogenesis and neurite branching in primary neurons
Overexpression of a neural-specific Rho family GTPase, cRac1B, selectively induces enhanced neuritogenesis and neurite branching in primary neurons
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DOI：
10.1083/jcb.142.3.815
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发表时间：
1998-08-10
影响因子：
7.8
通讯作者：
de Curtis, I
中科院分区：
文献类型：
--
作者：
Albertinazzi, C;Gilardelli, D;de Curtis, I
Rho家族GTP酶参与了轴突发生过程中的细胞骨架重组。我们最近发现了这个家族的一个新基因，cRac 1B，在鸡发育中的神经系统中特异性表达。该GTPase在原代神经元中过表达，以研究cRac 1B在神经元表型发育中的作用。cRac 1B的过表达诱导每个神经元神经突数量的增加，并显着增加神经突分支，而高度相关且普遍存在的cRac 1A GTPase的过表达并不明显影响神经元形态。此外，cRac 1B的非活性形式的表达显著抑制神经突形成。在神经元中观察到的cRac 1B作用的特异性在成纤维细胞中未观察到，其中两种GTP酶对细胞形态和肌动蛋白组织产生类似的影响，表明存在cRac 1B功能的细胞类型依赖性特异性。通过分析嵌合cRac 1A/cRac 1B蛋白的作用，对cRac 1B功能进行分子解剖，结果表明cRac 1B的COOH末端部分对诱导增加的神经突发生和神经突分支至关重要。考虑到cRac 1B表达在神经发育过程中的独特调节，我们的数据强烈支持cRac 1B在神经突发生过程中的重要作用，并揭示了不同Rho家族GTP酶功能特异性的新机制。
Rho family GTPases have been implicated in cytoskeletal reorganization during neuritogenesis. We have recently identified a new gene of this family, cRac1B, specifically expressed in the chicken developing nervous system. This GTPase was overexpressed in primary neurons to study the role of cRac1B in the development of the neuronal phenotype, Overexpression of cRac1B induced an increment in the number of neurites per neuron, and dramatically increased neurite branching, whereas overexpression of the highly related and ubiquitous cRac1A GTPase did not evidently affect neuronal morphology. Furthermore, expression of an inactive form of cRac1B strikingly inhibited neurite formation. The specificity of cRac1B action observed in neurons was not observed in fibroblasts, where both GTPases produced similar effects on cell morphology and actin organization, indicating the existence of a cell type-dependent specificity of cRac1B function. Molecular dissection of cRac1B function by analysis of the effects of chimeric cRac1A/cRac1B proteins showed that the COOH-terminal portion of cRac1B is essential to induce increased neuritogenesis and neurite branching. Considering the distinctive regulation of cRac1B expression during neural development, our data strongly support an important role of cRac1B during neuritogenesis, and they uncover new mechanisms underlying the functional specificity of distinct Rho family GTPases.