REGULATION OF AXONAL PROTEIN SYNTHESIS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 mRNA的亚细胞定位和翻译为细胞提供了局部可再生的蛋白质来源，以自主响应细胞外刺激。 对于神经元来说，这是至关重要的，因为神经元的细胞质和细胞膜可以延伸到细胞体尺寸的几百倍。 在发育神经元中的工作已经表明，局部蛋白质合成在轴突寻路中起作用，为轴突提供结构保护，并触发顺行和逆行轴突运输。 PI小组的研究表明，轴突蛋白质合成是由成年神经元的损伤触发的，再生轴突显示出特别强大的轴突内蛋白质合成。 这种局部的蛋白质合成代表了一种机制，可以被调节以促进成年神经系统中轴突的再生能力。 尽管轴突蛋白质合成的功能意义和新增加的兴趣，我们知道的太少的mRNA，其本地翻译的细胞外刺激调节。 我们的初步研究表明，成人轴突有潜力合成一个复杂的人口超过200种不同的蛋白质。 我们假设，轴突刺激改变本地化的蛋白质合成，通过指导特定的mRNA的运输到轴突室和本地控制的轴突翻译机器的活动。 这个BioAMS项目的目的是利用AMS的高灵敏度来量化再生轴突中蛋白质合成的调节方式。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Subcellular localization and translation of mRNAs provides cells with a locally renewable source of proteins to autonomously respond to extracellular stimuli. For neurons, this is critical since the cytoplasm and membranes of neurons can extend for several hundred times the dimensions of the cell body. Work in developing neurons has shown that localized protein synthesis plays a role in axonal pathfinding, provides structural protection to the axon, and triggers anterograde and retrograde axonal transport. Studies from the PI's group have shown that axonal protein synthesis is triggered by injury in adult neurons and that regenerating axons show particularly robust intra-axonal protein synthesis. This localized protein synthesis represents a mechanism that could be modulated to facilitate the regenerative capacity of axons in the adult nervous system. Despite the obvious functional significance of and newly increased interests in axonal protein synthesis, we know of excessively few mRNAs whose local translation is regulated by extracellular stimuli. Our preliminary studies indicate that adult axons have the potential to synthesize a complex population of more than 200 different proteins. 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 axonal translational machinery. The objective of this BioAMS project is to use the high sensitivity of AMS for quantifying how protein synthesis is regulated in regenerating axons.