Year: 2017
Type: review
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. Significance Statement Cellular 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.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Funders: Washington University in St. Louis, Foundation for Barnes-Jewish Hospital, Children's Discovery Institute, Hope Center for Neurological Disorders, National Institutes of Health, Center for Cellular Imaging, Washington University, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1186758267, G2202404319, G2355005229, G3219652903, G3693353605, University of Michigan Postbaccalaureate Research Education Program (UM PREP), G5746972746, Expanding Access to Planar Illumination Microscopy in a Neuroimaging Core, G5831677909, G63402963, DEVELOPMENT OF A NOVEL APPROACH TO STUDY ALTERNATIVE TRANSLATION IN THE CNS, TRANSLATION PROFILING AND NANOSCALE LOCALIZATION OF SYNAPTIC TRANSCRIPTS, G9000005743, G9000200356, G9000319192, Regulation of local translation in glia, Cancer Center Support Grant
OpenAlex ID: W2951270532