KINETICS OF AXONAL PROTEIN SYNTHESIS AND RNA TRANSPORT

轴突蛋白合成和 RNA 运输的动力学

• 批准号: 8169792
• 负责人: JEFFERY L TWISS
• 金额: $ 0.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169792
• 关键词: Affinity Chromatography; Axon; Biology; Brain; Communication; Computer Retrieval of Information on Scientific Projects Database; Data; Distal; Funding; Grant; Injury; Institution; Kinetics; Laboratories; Lead; Mass Spectrum Analysis; Messenger RNA; Natural regeneration; Neurons; Preparation; Process; Protein Biosynthesis; Protein Dynamics; Proteins; Proteome; Proteomics; Research; Research Personnel; Resources; Source; Spinal Cord; Traumatic Brain Injury; United States National Institutes of Health; Vertebral column; functional restoration; improved; injured; mRNA Precursor; novel strategies; protein complex; protein degradation; spinal cord and brain injury

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this project is to determine how the distal processes of nerve cells regulate their protein levels after injury. These 'axonal processes' are needed for long-range communication in the brain and spinal cord. If these processes are disrupted, communication ceases and function of the brain and spinal cord is lost. Improving regeneration of injured axonal processes will restore function to the brain and spinal column. Several lines of evidence indicate that distal axonal processes can autonomously regulate levels of proteins needed for regeneration through modulating synthesis and degradation of these proteins locally. Until recently we have had no means to dissect the proteome of regenerating axons, since the materials available for study are exceptionally limiting and most often contaminated with other cellular constituents. We will take advantage of an axonal preparation that our laboratory has developed and the high sensitivity proteomics applications of the UCSF Mass Spectrometry Facility to determine how the precursors of axonally synthesized proteins are targeted for transport into axons and what becomes of the protein products encoded by these precursors. We will use affinity purification of mRNA: protein complexes to identify the proteins needed for transport of the mRNA precursors into axons. Integrating these data with ongoing axonal mRNA profiling from our laboratory will provide a systematic view of protein dynamics of distal axons. Ultimately, these studies will provide us with a unique perspective of axonal biology that has not been feasible until now and should lead to novel strategies for accelerating regeneration after traumatic injury of the brain and spinal cord.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的目的是确定神经细胞的远端过程如何调节其损伤后其蛋白质水平。 这些“轴突过程”是在大脑和脊髓中的远程通信所需的。 如果这些过程受到破坏，则沟通停止和脊髓的功能就会丢失。 改善受伤的轴突过程的再生将恢复大脑和脊柱的功能。 几条证据表明，远端轴突过程可以自主调节通过调节这些蛋白质的合成和降解所需的再生所需的蛋白质水平。 直到最近，我们还没有能够剖析再生轴突的蛋白质组，因为可以进行研究的材料非常有限，并且通常被其他细胞成分污染。 我们将利用我们的实验室发展的轴突制备，并利用UCSF质谱设施的高灵敏度蛋白质组学应用，以确定如何将轴突合成蛋白的前体的靶向用于轴突的转运，以及这些前体编码的蛋白质产物的变化。 我们将使用mRNA的亲和力纯化：蛋白质复合物来鉴定将mRNA前体转运到轴突中所需的蛋白质。将这些数据与我们实验室的轴突mRNA分析相结合，将为远端轴突的蛋白质动力学提供系统的视野。 最终，这些研究将为我们提供轴突生物学的独特视角，轴突生物学直到现在一直是可行的，并且应该导致新的策略在大脑和脊髓创伤后加速再生。