Daly C, Ziff E B
Department of Biochemistry, Howard Hughes Medical Institute, New York University Medical Center, New York, New York 10016, USA.
J Neurosci. 1997 Apr 1;17(7):2365-75. doi: 10.1523/JNEUROSCI.17-07-02365.1997.
The regulated expression of synaptic vesicle (SV) proteins during development and the assembly of these proteins into functional SVs are critical aspects of nervous system maturation. We have examined the expression patterns of four SV proteins in embryonic hippocampal neurons developing in culture and have found that increases in the levels of these proteins result primarily from post-transcriptional regulation. Synaptotagmin I, vamp 2, and synapsin I proteins are synthesized at nearly constant rates as the neurons develop. However, these proteins are relatively unstable at early times in culture and undergo a progressive increase in half-life with time, possibly as a result of an increase in the efficiency with which they are incorporated into SVs. In contrast, synaptophysin is synthesized at a very low rate at early times in culture, and its rate of synthesis increases dramatically with time. The increase in synaptophysin synthesis is not simply the result of an increase in mRNA level, but is largely attributable to an increase in the rate of translational initiation. Despite the nearly constant rates of synthesis of synaptotagmin I, vamp 2, and synapsin I, we show that the number of SVs in these developing neurons increases, and that SV proteins are more efficiently targeted to SVs at later times in culture. Our results suggest that SV production during development is not limited by the rates of transcription of genes encoding the component proteins, thus allowing control of this process by cytoplasmic mechanisms, without signaling to the nucleus.
在发育过程中，突触小泡（SV）蛋白的表达调控以及这些蛋白组装成功能性突触小泡是神经系统成熟的关键方面。我们研究了培养的胚胎海马神经元中四种SV蛋白的表达模式，发现这些蛋白水平的增加主要源于转录后调控。随着神经元的发育，突触结合蛋白I、囊泡相关膜蛋白2（Vamp 2）和突触素I蛋白以几乎恒定的速率合成。然而，这些蛋白在培养早期相对不稳定，并且随着时间的推移半衰期逐渐增加，这可能是由于它们被整合到突触小泡中的效率提高所致。相比之下，突触素在培养早期的合成速率非常低，并且其合成速率随时间急剧增加。突触素合成的增加不仅仅是mRNA水平增加的结果，很大程度上归因于翻译起始速率的增加。尽管突触结合蛋白I、Vamp 2和突触素I的合成速率几乎恒定，但我们表明这些发育中的神经元中突触小泡的数量增加，并且在培养后期突触小泡蛋白更有效地靶向突触小泡。我们的结果表明，发育过程中突触小泡的产生不受编码组成蛋白的基因转录速率的限制，因此可以通过细胞质机制控制这一过程，而无需向细胞核发出信号。
