Regulation of axonal proteins synthesis

轴突间隔可以自主合成蛋白质，这一点已经被接受。这个当地人 翻译为轴突提供了一种可再生的蛋白质来源，以响应细胞外刺激。 PI研究小组的研究表明，轴突蛋白质合成是由神经损伤触发的，而且 尤其强大的蛋白质合成发生在再生的轴突中。这种局部的蛋白质合成 代表了一种很可能被利用来促进成人轴突再生的机制 神经系统。尽管轴突蛋白具有明显的功能意义和新的兴趣 对于合成，我们几乎不了解这个过程是如何调节的。我们的初步研究表明 成年轴突有可能合成由200多种不同蛋白质组成的复杂群体； 显然，选择在何时何地产生哪些蛋白质是有一定的特异性的。这样做的目的是 建议是确定这种轴突蛋白质合成是如何调节的。我们假设轴突 刺激通过引导特定的mRNAs的运输改变局部蛋白质合成 轴突间隔和局部控制轴突平移机械的活动。在目标1中， 我们将确定轴突引导线索和生长促进刺激如何改变轴突的特异性。 蛋白质合成。轴突运输和局部合成的作用将被确定。 鉴定出轴心合成的蛋白质。这些局部合成的生理后果 将讨论轴突生长中的蛋白质。在目标2中，我们将询问轴突如何控制合成 细胞器和膜蛋白以及这些途径与神经再生的功能相关性。 神经再生极其缓慢，很少成功。最近人们认识到，受伤的人 神经过程能够产生自己的蛋白质。我们的研究表明，这可能会被用于 以促进神经系统损伤后的恢复。这项拨款申请的目的是 确定神经突起中的局部蛋白质合成如何受到细胞外刺激的调节。

It has become accepted that the axonal compartment can autonomously synthesize proteins. This local translation provides the axon with a renewable source of proteins to respond to extracellular stimuli. Studies from the Pi's group have shown that axonal protein synthesis is triggered by neural injury and that particularly robust protein synthesis occurs in regenerating axons. This localized protein synthesis represents a mechanism that can likely be harnessed to facilitate the regeneration of axons in the adult nervous system. Despite the obvious functional significance and newly increased interests in axonal protein synthesis, we little understanding of how this process is regulated. Our preliminary studies indicate that adult axons have the potential to synthesize a complex population of more than 200 different proteins; there is clearly some specificity to choose which proteins are generated when and where. The objective of this proposal is to determine how this axonal protein synthesis is regulated. We hypothesize that axonal stimulation alters localized protein synthesis through both directing the transport of particular mRNAs into the axonal compartment and locally controlling the activity of the axonaltranslational machinery. In Aim 1, we will determine how axonal guidance cues and growth promoting stimuli modify specificity of axonal protein synthesis. The contributions of axonal transport vs. localized synthesis will be determined for each axonally synthesized protein identified. The physiological consequences of localized synthesis of these proteins in axonal growth will be addressed. In Aim 2 we will ask how the axon controls synthesis of organelle and membrane proteins and the functional relevance of these pathways to nerve regeneration. Nerve regeneration is abysmally slow and rarely successful. It has recently been recognized that injured nerve processes are capable of generating their own proteins. Our studies indicate that this may be used to enhance recovery after injury of the nervous system. The objective of this grant application is to determine how local protein synthesis in nerve processes is regulated by extracellular stimuli.