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Phosphorylation of MSI-1 is implicated in the regulation of associative memory in Caenorhabditis elegans.

Pavlina MastrandreasCsaba BoglariAndreas ArnoldFabian PeterDominique J-F de QuervainAndreas PapassotiropoulosAttila Stetak
Published in: PLoS genetics (2022)
The Musashi family of RNA-binding proteins controls several biological processes including stem cell maintenance, cell division and neural function. Previously, we demonstrated that the C. elegans Musashi ortholog, msi-1, regulates forgetting via translational repression of the Arp2/3 actin-branching complex. However, the mechanisms controlling MSI-1 activity during the regulation of forgetting are currently unknown. Here we investigated the effects of protein phosphorylation on MSI-1 activity. We showed that MSI-1 function is likely controlled by alterations of its activity rather than its expression levels. Furthermore, we found that MSI-1 is phosphorylated and using mass spectrometry we identified MSI-1 phosphorylation at three residues (T18, S19 and S34). CRISPR-based manipulations of MSI-1 phosphorylation sites revealed that phosphorylation is necessary for MSI-1 function in both short- and long-term aversive olfactory associative memory. Thus, our study provides insight into the mechanisms regulating memory-related MSI-1 activity and may facilitate the development of novel therapeutic approaches.
Keyphrases
  • stem cells
  • mass spectrometry
  • working memory
  • protein kinase
  • gene expression
  • genome wide
  • mesenchymal stem cells
  • high resolution
  • binding protein
  • capillary electrophoresis
  • high speed