REGULATION OF AXONAL PROTEIN SYNTHESIS

轴突蛋白合成的调节

• 批准号: 8362758
• 负责人: JEFFERY L TWISS
• 金额: $ 2.34万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362758
• 关键词: Adult; Axon; Axonal Transport; Cells; Complex; Cytoplasm; Dimensions; Funding; Genetic Translation; Grant; Injury; Membrane; Messenger RNA; National Center for Research Resources; Natural regeneration; Nervous system structure; Neurons; Play; Population; Principal Investigator; Protein Biosynthesis; Proteins; Regulation; Research; Research Infrastructure; Resource Development; Resources; Role; Source; Stimulus; Time; Translations; United States National Institutes of Health; Work; accelerator mass spectrometry; axonal pathfinding; cost; extracellular; interest; neuronal cell body; regenerative

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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，这一点至关重要，因为神经元的细胞质和细胞膜可以延伸到细胞体尺寸的数百倍。 发育神经元的研究表明，局部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损伤触发的，并且再生轴突显示出特别强大的轴突内蛋白质合成。 这种局部蛋白质合成代表了一种可以调节的机制，以促进成人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 mRNA 非常少。 我们的初步研究表明，成年轴突具有合成 200 多种不同蛋白质的复杂群体的潜力。 我们假设轴突刺激通过引导特定 mRNA 转运到轴突区室和局部控制轴突翻译机制的活动来改变局部蛋白质合成。 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。