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Activity dependent translation in astrocytes

View ORCID ProfileD. Sapkota, K. Sakers, Y. Liu, A.M. Lake, R. Khazanchi, R.R. Khankan, Y. Zhang, J.D. Dougherty
doi: https://doi.org/10.1101/2020.04.08.033027
D. Sapkota
1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
2Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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  • ORCID record for D. Sapkota
K. Sakers
1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
2Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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Y. Liu
1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
2Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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A.M. Lake
1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
2Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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R. Khazanchi
1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
2Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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R.R. Khankan
3Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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Y. Zhang
3Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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J.D. Dougherty
1Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
2Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
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  • For correspondence: jdougherty@genetics.wustl.edu
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Abstract

Gene expression requires two steps – transcription and translation – which can be regulated independently to allow nuanced, localized, and rapid responses to cellular stimuli. Neurons are known to respond transcriptionally and translationally to bursts of brain activity, and a transcriptional response to this activation has also been recently characterized in astrocytes. However, the extent to which astrocytes respond translationally is unknown. We tested the hypothesis that astrocytes also have a programmed translational response by characterizing the change in transcript ribosome occupancy in astrocytes using Translating Ribosome Affinity Purification subsequent to a robust induction of neuronal activity in vivo via acute seizure. We identified a reproducible change in transcripts on astrocyte ribosomes, highlighted by a rapid decrease in housekeeping transcripts, such as ribosomal and mitochondrial components, and a rapid increase in transcripts related to cytoskeleton, motor activity, ion transport, and cell communication. This indicates a dynamic response, some of which might be secondary to activation of Receptor Tyrosine Kinase signaling. Using acute slices, we quantified the extent to which individual cues and sequela of neuronal activity can activate translation acutely in astrocytes. This identified both BDNF and KCl as contributors to translation induction, the latter with both action-potential sensitive and insensitive components. Finally, we show that this translational response requires the presence of neurons, indicating the response is acutely or chronically non-cell autonomous. Regulation of translation in astrocytes by neuronal activity suggests an additional mechanism by which astrocytes may dynamically modulate nervous system functioning.

Competing Interest Statement

JDD has previously received royalties related to the TRAP method.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 09, 2020.
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Activity dependent translation in astrocytes
D. Sapkota, K. Sakers, Y. Liu, A.M. Lake, R. Khazanchi, R.R. Khankan, Y. Zhang, J.D. Dougherty
bioRxiv 2020.04.08.033027; doi: https://doi.org/10.1101/2020.04.08.033027
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Activity dependent translation in astrocytes
D. Sapkota, K. Sakers, Y. Liu, A.M. Lake, R. Khazanchi, R.R. Khankan, Y. Zhang, J.D. Dougherty
bioRxiv 2020.04.08.033027; doi: https://doi.org/10.1101/2020.04.08.033027

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