Schuman Erin M, Dynes Joseph L, Steward Oswald
Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
J Neurosci. 2006 Jul 5;26(27):7143-6. doi: 10.1523/JNEUROSCI.1796-06.2006.
The selective localization of protein synthetic machinery at postsynaptic sites makes it possible for the synthesis of particular proteins to be regulated by synaptic signals. Here we consider how the structure of the machinery constrains synthetic capacity and the evidence that mRNA translation is locally controlled by synaptic signals. Since the discovery of protein synthetic machinery at synaptic sites on dendrites (Steward and Levy, 1982), substantial progress has been made in identifying dendritic mRNAs and in showing that dendritic protein synthesis is critical for persistent synaptic modifications like long-term potentiation (LTP) and long-term depression (LTD). Although many pieces of the puzzle have been identified, major questions remain. Here we focus on one of the unknowns: how translational activity at synapses is regulated and whether regulation involves upregulation or downregulation of overall translation or differential regulation of the translation of particular transcripts. It is useful to begin by considering constraints imposed by the nature of the protein synthetic machinery at synapses.
蛋白质合成机制在突触后位点的选择性定位,使得特定蛋白质的合成能够受到突触信号的调控。在此,我们探讨该机制的结构如何限制合成能力,以及mRNA翻译受突触信号局部控制的证据。自发现树突突触位点存在蛋白质合成机制(Steward和Levy,1982年)以来,在鉴定树突mRNA以及证明树突蛋白质合成对于诸如长时程增强(LTP)和长时程抑制(LTD)等持续性突触修饰至关重要方面,已取得了重大进展。尽管谜团的许多部分已被解开,但主要问题依然存在。在此,我们聚焦于其中一个未知因素:突触处的翻译活性如何受到调控,以及这种调控涉及的是整体翻译的上调或下调,还是特定转录本翻译的差异调控。首先考虑突触处蛋白质合成机制的性质所施加的限制是很有必要的。