Astrocytes locally translate transcripts in their peripheral processes

Kristina Sakers, Allison M. Lake, Rohan Khazanchi, Rebecca Ouwenga, Michael J. Vasek, Adish Dani, and Joseph D. Dougherty: 2017 Proceedings of the National Academy of Sciences of the United States of America (PNAS) 114:19, pp. E3830-E3838 Read More

Abstract

Local translation in neuronal processes is key to the alteration of synaptic strength necessary for long-term potentiation, learning, and memory. Here, we present evidence that regulated de novo protein synthesis occurs within distal, perisynaptic astrocyte processes. Astrocyte ribosomal proteins are found adjacent to synapses in vivo, and immunofluorescent detection of peptide elongation in acute slices demonstrates robust translation in distal processes. We have also developed a biochemical approach to define candidate transcripts that are locally translated in astrocyte processes. Computational analyses indicate that astrocyte-localized translation is both sequence-dependent and enriched for particular biological functions, such as fatty acid synthesis, and for pathways consistent with known roles for astrocyte processes, such as GABA and glutamate metabolism. These transcripts also include glial regulators of synaptic refinement, such as Sparc. Finally, the transcripts contain a disproportionate amount of a binding motif for the quaking RNA binding protein, a sequence we show can significantly regulate mRNA localization and translation in the astrocytes. Overall, our observations raise the possibility that local production of astrocyte proteins may support microscale alterations of adjacent synapses.

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Posted on June 1, 2017
Posted in: HPAN, Neurodegeneration, Neurogenetics & Transcriptomics, Publications Authors: ,