Post-transcriptional regulation of synaptic vesicle protein expression and the developmental control of synaptic vesicle formation

Abstract

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 1, 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.