The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity
The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity
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DOI：
10.1038/nn1295
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发表时间：
2004-09-01
影响因子：
25
通讯作者：
Püschel, AW
中科院分区：
文献类型：
--
作者：
Schwamborn, JC;Püschel, AW
极化形态的建立是单轴突多树突神经元分化的重要步骤。在培养的大鼠海马神经元中，从几个最初难以区分的神经突中选择一个成为轴突。磷脂酰肌醇3，4，5-三磷酸和进化上保守的Par复合物（包括Par 3、Par 6和非典型PKC（aPKC）如PKC λ或PKCzeta）都参与轴突特化。然而，建立细胞不对称性的初始信号和随后将其转化为结构变化的途径仍有待阐明。在这里，我们表明，本地化的GTTRIP 1B的一个单一的神经突的尖端是决定性的一步，在确定哪一个神经突成为轴突。使用GTPase突变体和RNA干扰，我们发现Rap 1B对于启动Cdc 42和Par复合物上游轴突的发育是必要且足够的。
The establishment of a polarized morphology is an essential step in the differentiation of neurons with a single axon and multiple dendrites. In cultured rat hippocampal neurons, one of several initially indistinguishable neurites is selected to become the axon. Both phosphatidylinositol 3,4,5-trisphosphate and the evolutionarily conserved Par complex ( comprising Par3, Par6 and an atypical PKC (aPKC) such as PKClambda or PKCzeta) are involved in axon specification. However, the initial signals that establish cellular asymmetry and the pathways that subsequently translate it into structural changes remain to be elucidated. Here we show that localization of the GTPase Rap1B to the tip of a single neurite is a decisive step in determining which neurite becomes the axon. Using GTPase mutants and RNA interference, we found that Rap1B is necessary and sufficient to initiate the development of axons upstream of Cdc42 and the Par complex.