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轴突中mRNA运输的新见解。

New insights into mRNA trafficking in axons.

作者信息

Gumy Laura F, Katrukha Eugene A, Kapitein Lukas C, Hoogenraad Casper C

机构信息

Division of Cell Biology, University of Utrecht, Padualaan 8, 3584CH, Utrecht, The Netherlands.

出版信息

Dev Neurobiol. 2014 Mar;74(3):233-44. doi: 10.1002/dneu.22121. Epub 2013 Sep 30.

Abstract

In recent years, it has been demonstrated that mRNAs localize to axons of young and mature central and peripheral nervous system neurons in culture and in vivo. Increasing evidence is supporting a fundamental role for the local translation of these mRNAs in neuronal function by regulating axon growth, maintenance and regeneration after injury. Although most mRNAs found in axons are abundant transcripts and not restricted to the axonal compartment, they are sequestered into transport ribonucleoprotein particles and their axonal localization is likely the result of specific targeting rather than passive diffusion. It has been reported that long-distance mRNA transport requires microtubule-dependent motors, but the molecular mechanisms underlying the sorting and trafficking of mRNAs into axons have remained elusive. This review places particular emphasis on motor-dependent transport of mRNAs and presents a mathematical model that describes how microtubule-dependent motors can achieve targeted trafficking in axons. A future challenge will be to systematically explore how the numerous axonal mRNAs and RNA-binding proteins regulate different aspects of specific axonal mRNA trafficking during development and after regeneration.

摘要

近年来,已证实信使核糖核酸(mRNA)在体外培养和体内均定位于年轻及成熟的中枢和外周神经系统神经元的轴突。越来越多的证据支持这些mRNA的局部翻译通过调节轴突生长、维持及损伤后的再生在神经元功能中发挥重要作用。尽管在轴突中发现的大多数mRNA是丰富的转录本,并非局限于轴突区室,但它们被隔离到运输核糖核蛋白颗粒中,其轴突定位可能是特异性靶向的结果,而非被动扩散。据报道,长距离mRNA运输需要微管依赖型马达,但mRNA分选和运输到轴突的分子机制仍不清楚。本综述特别强调了mRNA的马达依赖型运输,并提出了一个数学模型,描述微管依赖型马达如何在轴突中实现靶向运输。未来的一个挑战将是系统地探索众多轴突mRNA和RNA结合蛋白如何在发育过程和再生后调节特定轴突mRNA运输的不同方面。

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