Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay.
Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay.
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DOI：
10.1016/j.cell.2013.04.056
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发表时间：
2013-06-06
期刊：
影响因子：
64.5
通讯作者：
Jaffrey SR
中科院分区：
文献类型：
--
作者：
Colak D;Ji SJ;Porse BT;Jaffrey SR
生长锥使轴突能够通过响应细胞外信号分子而导航到其目标。生长锥反应部分由轴突mRNA的局部翻译介导。然而，调节本地翻译的机制知之甚少。在这里，我们表明，Robo3.2，狭缝家庭的指导线索的受体，是本地合成的连合神经元的轴突内。当轴突穿过脊髓中线时，Robo3.2翻译由地板来源的信号诱导。Robo3.2也是无义介导的mRNA衰变（NMD）途径的预测靶点。我们发现，NMD调节Robo3.2合成诱导降解的Robo3.2转录轴突遇到地板。缺乏NMD蛋白的连合神经元在穿过中线后表现出异常的轴突轨迹，这与Robo3.2表达的失调一致。这些数据表明，局部翻译是由mRNA的稳定性，NMD的作用局部影响轴突寻路。
Growth cones enable axons to navigate towards their targets by responding to extracellular signaling molecules. Growth cone responses are mediated in part by the local translation of axonal mRNAs. However, the mechanisms that regulate local translation are poorly understood. Here we show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3.2 expression. These data show that local translation is regulated by mRNA stability, and that NMD acts locally to influence axonal pathfinding.
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