Astrocytes locally translate transcripts in their peripheral processes

Abstract

Local translation in neuronal processes is key to the alteration of synaptic strength that contributes to long term potentiation and learning and memory. Here, we present evidence that astrocytes have ribosomes in their peripheral and perisynaptic processes, and that de novo protein synthesis occurs in the astrocyte periphery. We also developed a new biochemical approach to profile and define a set of candidate transcripts that are locally translated in astrocyte processes, several of which were validated in vivo using in situ hybridization of sparsely labeled cells. Computational analyses indicate that localized translation is both sequence dependent and enriched for particular biological functions. This includes novel pathways such as fatty acid synthesis as well as pathways consistent with known roles for astrocyte processes, such as GABA and glutamate metabolism. Finally, enriched transcripts also include key glial regulators of synaptic refinement, suggesting that local production of astrocyte proteins may support microscale alterations of adjacent synapses.\n\nSignificance StatementCellular compartments are specialized for particular functions. In astrocytes, the peripheral processes, particularly near synapses, contain proteins specialized for reuptake of neurotransmitters and ions, and have been shown to alter their morphology in response to activity. Regulated transport of a specific subset of nuclear-derived mRNAs to particular compartments is thought to support the specialization of these compartments and allow for local regulation of translation. In neurons, local translation near activated synapses is thought to generate the proteins needed for the synaptic alterations that constitute memory. We demonstrate that astrocytes also have sequence-dependent local translation in their peripheral processes, including transcripts with roles in regulating synapses. This suggests local translation in astrocyte processes may also play a role in modulating synapses.