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Astrocytes locally translate transcripts in their peripheral processes
Open accessPublished version of a preprint
Abstract
Significance: Cellular compartments are specialized for particular functions. In astrocytes, the peripheral, perisynaptic processes 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 specific 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, and identify one mechanism regulating this translation. These findings suggest local translation in astrocyte processes may play a role in synapse modulation.
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“signifying local translation, a scenario described for Gfap and other key astrocyte genes35, 36.”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [35]
Experimental — accuracy not yet measuredIn the citing paper
“We further confirmed that HA-tagged ribosomes are present throughout the astrocyte, including distal processes where local translation occurs (Figure 1G; Sakers et al., 2017).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Sakers et al., 2017
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Spatially resolved, highly multiplexed RNA profiling in single cells
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Tripartite synapses: glia, the unacknowledged partner
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Cited by
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Cell Biology of Astrocyte-Synapse Interactions
Allen, N. J., & Eroglu, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.056 · Cited by 1,098
“Astrocytes indirectly regulate synapse elimination via the secretion of transforming growth factor b (TGF-b), which upregulates C1q in neurons, leading to tagging of synapses for elimination by phagocytosis by microglia (Figure 2C; Bialas and Stevens, 2013; Schafer et al., 2012).”
Identification of region-specific astrocyte subtypes at single cell resolution
Batiuk, M. Y., Martirosyan, A., Wahis, J., de Vin, F., Marneffe, C., Kusserow, C., Koeppen, J., Viana, J. F., Oliveira, J. F., Voet, T., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14198-8 · Cited by 805
Astrocyte function from information processing to cognition and cognitive impairment
Santello, M., Toni, N., & Volterra, A. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0325-8 · Cited by 737
The aging astrocyte transcriptome from multiple regions of the mouse brain.
Boisvert, M. M., Erikson, G. A., Shokhirev, M. N., & Allen, N. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.039 · Cited by 702
“We further confirmed that HA-tagged ribosomes are present throughout the astrocyte, including distal processes where local translation occurs (Figure 1G; Sakers et al., 2017).”
BackgroundDejanovic, B., Wu, T., Tsai, M.-C., Graykowski, D., Gandham, V. D., Rose, C. M., Bakalarski, C. E., Ngu, H., Wang, Y., Pandey, S., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00281-1 · Cited by 341
Metadata
- Authors
- Sakers, K., Lake, A. M., Khazanchi, R., Ouwenga, R., Vasek, M. J., Dani, A., & Dougherty, J. D.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Dougherty, Joseph D.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-04-24
- Volume
- 114
- Issue
- 19
- Pages
- E3830-E3838
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5441704
- OpenAlex
- W2951270532
- Cited by
- 202
- References
- 72
- Citations by year
- 2026: 24 · 2025: 17 · 2024: 20 · 2023: 25 · 2022: 22 · 2021: 27 · 2020: 20 · 2019: 20 · 2018: 19 · 2017: 8
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Children's Discovery Institute (MD-II-2013-269)
- HHS | National Institutes of Health (DA038458-01, MH099798-01)
- WUSTL Interface of Psychology Neuroscience and Genetics Training Grant (5T32 GM081739)
- WUSTL Neurosciences Program Training Grant (T32 GM008151)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- astrocytes, local translation, mRNA transport, synaptic regulation
- MeSH terms
- Animals, Astrocytes, Cell Nucleus, Humans, Memory, Neurons, RNA, Messenger, Synapses, Protein Biosynthesis
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