An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration.
An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration.
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DOI：
10.1038/ncomms4405
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发表时间：
2014-02-27
影响因子：
16.6
通讯作者：
Guillemot, Francois
中科院分区：
文献类型：
--
作者：
Azzarelli, Roberta;Pacary, Emilie;Garg, Ritu;Garcez, Patricia;van den Berg, Debbie;Riou, Philippe;Ridley, Anne J.;Friedel, Roland H.;Parsons, Maddy;Guillemot, Francois
由前神经因子Neurog 2和Ascl 1启动的转录程序控制胚胎大脑皮层神经发生的连续步骤。先前的工作表明，前神经因子也通过诱导小GTP结合蛋白如Rnd 2和Rnd 3的表达赋予皮层神经元迁移行为。然而，放射状迁移的方向性表明，迁移神经元也响应细胞外信号调节途径。在这里，我们表明丛蛋白B2受体与Rnd 3在物理和功能上相互作用，并刺激迁移皮层神经元中的RhoA活性。丛状蛋白B2与p190 RhoGAP竞争结合Rnd 3，从而阻断Rnd 3介导的RhoA抑制，并且还募集RhoGEF以直接刺激RhoA活性。因此，细胞外丛状蛋白信号通路和细胞内Ascl 1-Rnd 3通路之间的相互作用决定了适合皮质神经元迁移的RhoA活性水平。 小GTP酶Rnd 2和Rnd 3作用于前神经因子的下游，以控制小鼠胚胎大脑皮层中神经元的迁移行为。在这里，Azzarelli等人表明，Rnd 3与脑信号蛋白受体丛蛋白B2的结合微调了皮层神经元迁移所需的活性RhoA水平。
A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to cortical neurons by inducing the expression of the small GTP-binding proteins such as Rnd2 and Rnd3. However, the directionality of radial migration suggests that migrating neurons also respond to extracellular signal-regulated pathways. Here we show that the Plexin B2 receptor interacts physically and functionally with Rnd3 and stimulates RhoA activity in migrating cortical neurons. Plexin B2 competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity. Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity appropriate for cortical neuron migration. The small GTPases Rnd2 and Rnd3 act downstream of proneural factors to control the migrating behaviour of neurons in the mouse embryonic cerebral cortex. Here, Azzarelli et al. show that Rnd3 binding to the semaphorin receptor PlexinB2 fine-tunes the levels of active RhoA required for cortical neuron migration.
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