Yoon Byung C, Zivraj Krishna H, Holt Christine E
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.
Results Probl Cell Differ. 2009;48:269-88. doi: 10.1007/400_2009_5.
Axons and their growth cones are specialized neuronal sub-compartments that possess translation machinery and have distinct messenger RNAs (mRNAs). Several classes of mRNAs have been identified using candidate-based, as well as unbiased genome-wide-based approaches. Axonal mRNA localization serves to regulate spatially the protein synthesis; thereby, providing axons with a high degree of functional autonomy from the soma during axon pathfinding. Importantly, de novo protein synthesis in navigating axonal growth cones is necessary for chemotropic responses to various axon guidance cues. This chapter discusses the molecular components involved in regulating axonal mRNA trafficking, targeting, and translation, and focuses on RNA binding proteins (RNBPs) and microRNAs. The functional significance of local mRNA translation in the directional response of growth cones to a gradient is highlighted along with the downstream signaling events that mediate local protein synthesis. The view that emerges is that local translation is tightly coupled to extracellular cues, enabling growth cones to respond to new signals with exquisite adaptability and spatiotemporal control.
轴突及其生长锥是特殊的神经元亚区室,它们拥有翻译机制并具有独特的信使核糖核酸(mRNA)。已经使用基于候选基因以及基于全基因组无偏差的方法鉴定出了几类mRNA。轴突mRNA定位用于在空间上调节蛋白质合成;从而在轴突寻路过程中为轴突提供高度的功能自主性,使其独立于胞体。重要的是,在轴突生长锥导航过程中的从头蛋白质合成对于对各种轴突导向线索的趋化反应是必需的。本章讨论了参与调节轴突mRNA运输、靶向和翻译的分子成分,并重点关注RNA结合蛋白(RBP)和微小RNA。文中强调了局部mRNA翻译在生长锥对梯度的定向反应中的功能意义,以及介导局部蛋白质合成的下游信号事件。由此形成的观点是,局部翻译与细胞外信号紧密耦合,使生长锥能够以精确的适应性和时空控制对新信号做出反应。