Neurons exhibit a unique degree of spatial compartmentalization and are able to maintain and remodel their proteomes independently from the cell body. While much effort has been devoted to understanding the capacity and role for local protein synthesis in dendrites and spines, local mRNA translation in mature axons, projecting over distances up to a meter, has received much less attention. Also, little is known about the spatio-temporal dynamics of axonal and dendritic gene expression as function of mRNA abundance, protein synthesis and degradation. Here, we summarize key recent findings that have shaped our knowledge of the precise location of local protein production and discuss unique strategies used by neurons to shape presynaptic and postsynaptic proteomes.
Local translation in neuronal processes
Spatio-temporal control of mRNA translation in neuronal processes – a conceptual view.
(a) While translation of specific mRNAs by single or few ribosomes may suffice to fuel synapses with long-lived and low abundant proteins,
increased ribosome recruitment could be required for maintaining the local homeostasis of abundant, less stable proteins.
(b) 50 UTR diversity can provide means to differentially regulate the translational efficiency of the same transcript species. Cis-regulatory elements
embedded within the 50 UTR dynamically interact with trans-acting factors to regulate the rate and the site of translation initiation. Initiation from
alternative translation start sites could promote the production of various protein isoforms that may differ in their function or localization.
(c) Serving as platform for microRNAs and RBPs, 30 UTR isoforms may expand the potential for differential translational regulation of the same
mRNA species. Synaptic stimulation could induce a local 30 UTR shortening of selective mRNAs, which may enhance their translational efficiency.
(d) Localized translation of ribosomal proteins may allow in-situ tailoring of the ribosome composition. This direct specialization of the translational
machinery itself could control the translation of selective transcript subsets in response to specific synaptic stimuli.
Max Planck Institute for Brain Research
