POSTTRANSCRIPTIONAL REGULATION OF SYNAPTIC VESICLE PROTEIN EXPRESSIONAND THE DEVELOPMENTAL CONTROL OF SYNAPTIC VESICLE FORMATION

The regulated expression of synaptic vesicle (SV) proteins during deve lopment and the assembly of these proteins into functional SVs are cri tical aspects of nervous system maturation. We have examined the expre ssion patterns of four SV proteins in embryonic hippocampal neurons de veloping in culture and have found that increases in the levels of the se proteins result primarily from post-transcriptional regulation. Syn aptotagmin I, vamp 2, and synapsin I proteins are synthesized at nearl y constant rates as the neurons develop. However, these proteins are r elatively 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 contra st, synaptophysin is synthesized at a very low rate at early times in culture, and its rate of synthesis increases dramatically with time. T he 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 rate s of synthesis of synaptotagmin I, vamp 2, and synapsin I, we show tha t the number of SVs in these developing neurons increases, and that SV proteins are more efficiently targeted to SVs at later times in cultu re. Our results suggest that SV production during development is not l imited by the rates of transcription of genes encoding the component p roteins, thus allowing control of this process by cytoplasmic mechanis ms, without signaling to the nucleus.