Synaptic regulation of translation of dendritic mRNAs

Abstract

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.

Figure 1.

Approximate sizes of representative dendritic mRNAs and translational elements at synaptic sites on dendrites. The drawing illustrates the approximate size range of spine synapses that would be found in rat forebrain structures such as the hippocampus and cerebral cortex. The lines represent the approximate length of representative dendritic mRNAs if they were straightened out. Shading indicates the length and position of the coding region.