Protein synthesis and processing in cytoplasmic microdomains beneath postsynaptic sites on CNS neurons

Abstract

Recent studies have shown that protein synthetic machinery consisting of polyribosomes and associated membranous cisterns is selectively localized beneath synaptic sites on neurons. In the present paper, the role of this machinery in neuronal function will be considered. We will:

• 1. Summarize the studies that characterize the polyribosomes and define their associations with membranous cisterns. Taken together, these observations suggest the existence of a system for the synthesis and posttranslational processing of proteins at individual synaptic sites;

• 2. Review the evidence that the protein synthetic machinery is particularly prominent during the initial formation of synaptic contacts (during early development), and during lesion-induced synaptogenesis in mature animals. These observations have led to the hypothesis that the polyribosomes produce proteins that play a role in the formation of the synaptic junction;

• 3. Review evidence that supports the hypothesis that there is a local synthesis of protein within dendrites, as well as local glycosylation;

• 4. Describe the evidence suggesting that at least some of the protein constituents of the synaptic junction itself are synthesized locally; and

• 5. Descibe our studies that reveal a mechanism for selective dendritic transport of RNA; this transport mechanism permits the delivery of RNA to postsynaptic sites throughout the dendritic arbor.

We will advance the hypothesis that neurons position protein synthetic machinery together with the mRNA's that are appropriate for particular synapses beneath synaptic contact regions. At the synaptic site, this machinery could then direct the synthesis of particular proteins that are critical for synapse formation or maintenance. The positioning of protein synthetic machinery at postsynaptic sites permits a rapid local regulation of the production of key proteins by events at individual synapses.