Activity-dependent translation dynamically alters the proteome of the perisynaptic astrocyte process

Darshan Sapkota, Mandy S.J. Kater, Kristina Sakers, Kayla R. Nygaard, Yating Liu, Sarah K. Koester, Stuart B. Fass, Allison M. Lake, Rohan Khazanchi, Rana R. Khankan, Mitchell C. Krawczyk, August B. Smit, Susan E. Maloney, Mark H.G. Verheijen, Ye Zhang, Joseph D. Dougherty

Research output: Contribution to journalArticlepeer-review

Abstract

Within eukaryotic cells, translation is regulated independent of transcription, enabling nuanced, localized, and rapid responses to stimuli. Neurons respond transcriptionally and translationally to synaptic activity. Although transcriptional responses are documented in astrocytes, here we test whether astrocytes have programmed translational responses. We show that seizure activity rapidly changes the transcripts on astrocyte ribosomes, some predicted to be downstream of BDNF signaling. In acute slices, we quantify the extent to which cues of neuronal activity activate translation in astrocytes and show that this translational response requires the presence of neurons, indicating that the response is non-cell autonomous. We also show that this induction of new translation extends into the periphery of astrocytes. Finally, synaptic proteomics show that new translation is required for changes that occur in perisynaptic astrocyte protein composition after fear conditioning. Regulation of translation in astrocytes by neuronal activity suggests an additional mechanism by which astrocytes may dynamically modulate nervous system functioning.

Original languageEnglish
Article number111474
JournalCell Reports
Volume41
Issue number3
DOIs
StatePublished - Oct 18 2022

Keywords

  • CP: Neuroscience
  • TRAP
  • astrocyte
  • regulation
  • seizure
  • translation

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