中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (10): 1560-1562.doi: 10.4103/1673-5374.165264

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

核内蛋白的轴突内位移:支持神经突生长与再生

  

  • 收稿日期:2015-06-19 出版日期:2015-10-28 发布日期:2015-10-28
  • 基金资助:

    Prof. Twiss实验室关于轴突转译工作的研究是由美国国立卫生研究院(P01-NS055976和R01-NS041596),美国国家科学基金会(MCB-1020970),Dr. Miriam 和Sheldon G. Adelson医学研究基金会,以及国防部/美国陆军医学研究与发展事务部(OR120042)资助。作者还接受到南卡罗来纳大学提供的南卡罗来纳州智能项目资助。

Old dogs with new tricks: intra-axonal translation of nuclear proteins

Jeffery L. Twiss*, Tanuja T. Merianda   

  1. Department of Biological Sciences, University of South Carolina,Columbia, SC, USA (Twiss JL)
    Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA (Twiss JL, Merianda TT)
  • Received:2015-06-19 Online:2015-10-28 Published:2015-10-28
  • Contact: Jeffery L. Twiss, M.D., Ph.D.,twiss@mailbox.sc.edu.
  • Supported by:

    Work on axonal translation in the Twiss lab is supported by funds from National Institutes of Health (P01-NS055976 and R01-NS041596), National Science Foundation (MCB-1020970), Dr. Miriam and Sheldon G. Adelson Medical Research Foundation,
    and the Department of Defense/US Army Medical Research and Development (OR120042). JLT is an Endowed Chair in Childhood Neurotherapeutics in the South Carolina SmartState Program at the University of South Carolina.

摘要:

许多新类型的极化真核细胞已经被引导隔离合成一些蛋白亚群到胞浆域中远离它们的细胞核。对神经元来说,这些间隔可以有超过细胞体直径长度数十甚至数千倍的褶皱。局部存在于突触或生长锥的信使核糖核酸通过激活位移可以带来比转运来自细胞体新蛋白更快的反应。既然多种蛋白拷贝可以通过连续的位移从单一的信使核糖核酸中产生,那么就能量消耗而言,神经元就好像从这一机制中得到益处。局部蛋白合成也可以更加有效地安置一个蛋白靠近作用部位或甚至是给蛋白带来非预计的新功能。蛋白可以通过蛋白间的相互作用呈现出不同的功能,所以通过局部的信使核糖核酸给蛋白编码可以凭借他们时空场景的合成从细胞体编码的蛋白中获取不同功能。以HMGN5和HMGB1二性霉素信使核糖核酸为目标进入神经突也可被用作一种方法,通过隔离这些信使核糖核酸远离细胞核外周区域并且确保两种功能性独特的蛋白种群来克服它们编码的核定位信号。出于这种考虑,信使核糖核酸与顺式作用元件相互作用以用来把HMGN5和HMGB1二性霉素信使核糖核酸作为目标进入轴突和树突,此事件可以作为诱发事件并据此表明通过局部信使核糖核酸产生的蛋白,其功能是支持神经突生长与再生。

Abstract:

Many different types of polarized eukaryotic cells have been shown to segregatesynthesis for some protein subpopulations to cytoplasmic domains distant from their nucleus. For neurons, these distances can be tens-to-thousands fold more than the diameter of the cell body. Both axons and dendrites make use of this localized protein synthesis to bring autonomy to these far reaches of the cytoplasm. Oftentimes this local mRNA translation is used to mount a rapid response to extracellular stimuli encountered by the distal axon and dendrite. Indeed, activating translation of mRNAs residing locally at the synapse or growth cone brings a much more rapid response than could be achieved by transporting new proteins from the cell body. The neuron likely reapsa cost benefit from this mechanism in terms of energy consumption, since multiple protein copies can be generated from a single mRNA through sequential rounds of translation. Localized protein synthesis could also more effectively positiona protein near its site of action or even bring an unanticipated novel function to the protein.