Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Nat Rev Neurosci. 2012 Apr 13;13(5):308-24. doi: 10.1038/nrn3210.
mRNAs can be targeted to specific neuronal subcellular domains, which enables rapid changes in the local proteome through local translation. This mRNA-based mechanism links extrinsic signals to spatially restricted cellular responses and can mediate stimulus-driven adaptive responses such as dendritic plasticity. Local mRNA translation also occurs in growing axons where it can mediate directional responses to guidance signals. Recent profiling studies have revealed that both growing and mature axons possess surprisingly complex and dynamic transcriptomes, thereby suggesting that axonal mRNA localization is highly regulated and has a role in a broad range of processes, a view that is increasingly being supported by new experimental evidence. Here, we review current knowledge on the roles and regulatory mechanisms of axonal mRNA translation and discuss emerging links to axon guidance, survival, regeneration and neurological disorders.
mRNA 可以被靶向到特定的神经元亚细胞区域,这使得通过局部翻译可以快速改变局部蛋白质组。这种基于 mRNA 的机制将外部信号与空间受限的细胞反应联系起来,并可以介导刺激驱动的适应性反应,如树突可塑性。局部 mRNA 翻译也发生在生长的轴突中,它可以介导对导向信号的定向反应。最近的分析研究表明,生长中的和成熟的轴突都具有惊人的复杂和动态的转录组,这表明轴突 mRNA 的定位受到高度调控,并且在广泛的过程中具有作用,这一观点越来越多地得到新的实验证据的支持。在这里,我们回顾了关于轴突 mRNA 翻译的作用和调节机制的现有知识,并讨论了与轴突导向、存活、再生和神经疾病的新联系。