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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的目的是确定损伤后神经细胞的远端突起如何调节其蛋白质水平。这些“轴突”是大脑和脊髓进行远程通讯所必需的。如果这些过程被破坏，沟通就会停止，大脑和脊髓的功能就会丧失。促进受损轴突的再生将恢复大脑和脊柱的功能。一些证据表明，远端轴突可以通过调节局部蛋白质的合成和降解来自主调节再生所需的蛋白质水平。直到最近，我们还没有办法剖析再生轴突的蛋白质组，因为可供研究的材料非常有限，而且经常被其他细胞成分污染。我们将利用我们实验室开发的轴突制备和加州大学旧金山分校质谱仪的高灵敏度蛋白质组学应用来确定轴向合成蛋白质的前体是如何被定位为运输到轴突中的，以及这些前体编码的蛋白质产物会发生什么。我们将使用亲和纯化的信使核糖核酸：蛋白质复合体来鉴定将信使核糖核酸前体运输到轴突所需的蛋白质。将这些数据与我们实验室正在进行的轴突mRNA图谱分析相结合，将提供远端轴突蛋白质动力学的系统视图。最终，这些研究将为我们提供一个独特的轴突生物学视角，这到目前为止还不可行，应该会导致加速脑和脊髓创伤后再生的新策略。