REGULATION OF AXONAL PROTEIN SYNTHESIS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 MRNAs的亚细胞定位和翻译为细胞提供了一种局部可再生的蛋白质来源，以自主地对细胞外刺激做出反应。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的数百倍大小。对神经元发育的研究表明，局部的蛋白质合成在轴突寻路中发挥作用，为轴突提供结构保护，并触发轴突的顺行和逆行运输。PI的研究小组的研究表明，轴突蛋白质合成是由成年神经元的损伤触发的，再生的轴突显示出特别强劲的轴突内蛋白质合成。这种局部的蛋白质合成代表了一种可以被调节的机制，以促进成年神经系统中轴突的再生能力。尽管轴突蛋白合成具有明显的功能意义和新的兴趣，但我们知道其局部翻译受细胞外刺激调节的mRNAs过少。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。我们假设轴突刺激通过引导特定的mRNAs进入轴突间室和局部控制轴突翻译机制的活动来改变局部的蛋白质合成。该BioAMS项目的目标是利用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.