Martin Kelsey C, Zukin R Suzanne
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California 90095-1761, USA.
J Neurosci. 2006 Jul 5;26(27):7131-4. doi: 10.1523/JNEUROSCI.1801-06.2006.
It is now widely accepted that mRNAs localize to dendrites and that translation of these mRNAs is regulated in response to neuronal activity. Recent studies have begun to reveal the underpinnings of these processes and to underscore the importance of local protein synthesis to synaptic remodeling and plasticity. When Steward and Levy (1982) first reported their observation of polyribosomes at the base of spines, the prevailing view was that all proteins were synthesized in the cell body and then transported to distal compartments of neurons. Steward and Levy's discovery, however, raised the intriguing possibility that mRNAs could be transported to synapses and locally translated in response to synaptic stimulation. This provided an elegant mechanism for spatially restricting gene expression within the neuron, such that individual synapses could independently regulate their morphology and efficacy, in a persistent, protein synthesis-dependent manner, in response to specific stimuli. It is now widely accepted that mRNAs do localize to dendrites and that translation of these mRNAs contributes to synaptic plasticity. As is evident from the collection of Mini-Reviews on dendritic protein synthesis in this issue of The Journal of Neuroscience, the field has evolved to focus on a series of key questions, including the following: (1) what mRNAs are present in dendrites? (2) How are these mRNAs transported from the nucleus into the dendrite? (3) How is translation of these mRNAs regulated by neuronal activity? and (4) What is the function of local translation of specific transcripts? In this brief introductory overview, we will consider each of these questions in turn.
现在人们广泛接受的观点是,mRNA定位于树突,并且这些mRNA的翻译受神经元活动的调节。最近的研究已经开始揭示这些过程的基础,并强调局部蛋白质合成对突触重塑和可塑性的重要性。当斯图尔特和利维(1982年)首次报道他们在棘突基部观察到多核糖体时,当时盛行的观点是所有蛋白质都在细胞体中合成,然后运输到神经元的远端部分。然而,斯图尔特和利维的发现提出了一个有趣的可能性,即mRNA可以被运输到突触并在突触刺激下进行局部翻译。这为在神经元内空间限制基因表达提供了一种巧妙的机制,使得单个突触能够以持续的、依赖蛋白质合成的方式,响应特定刺激,独立调节其形态和效能。现在人们广泛接受的观点是,mRNA确实定位于树突,并且这些mRNA的翻译有助于突触可塑性。从本期《神经科学杂志》关于树突蛋白合成的小型综述集中可以明显看出,该领域已经发展到关注一系列关键问题,包括以下问题:(1)树突中存在哪些mRNA?(2)这些mRNA如何从细胞核运输到树突?(3)这些mRNA的翻译如何受神经元活动调节?以及(4)特定转录本的局部翻译有什么功能?在这个简短的介绍性概述中,我们将依次考虑每个问题。