O-GlcNAcase contributes to cognitive function in Drosophila

Villo Muha, Michaela Fenckova, Andrew Ferenbach, Marica Catinozzi, Ilse Eidhof, Erik Storkebaum, Annette Schenck, Daan van Aalten (Lead / Corresponding author)

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Abstract

O-GlcNAcylation is an abundant post-translational modification in neurons. In mice, an increase in O-GlcNAcylation leads to defects in hippocampal synaptic plasticity and learning. O-GlcNAcylation is established by two opposing enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). To investigate the role of OGA in elementary learning, we generated catalytically inactive and precise knockout Oga alleles (OgaD133N and OgaKO , respectively) in Drosophila melanogaster Adult OgaD133N and OgaKO flies lacking O-GlcNAcase activity showed locomotor phenotypes. Importantly, both Oga lines exhibited deficits in habituation, an evolutionarily conserved form of learning, highlighting that the requirement for O-GlcNAcase activity for cognitive function is preserved across species. Loss of O-GlcNAcase affected a number of synaptic boutons at the axon terminals of larval neuromuscular junction. Taken together, we report behavioral and neurodevelopmental phenotypes associated with Oga alleles and show that Oga contributes to cognition and synaptic morphology in Drosophila.

Original languageEnglish
Pages (from-to)8636-8646
Number of pages12
JournalJournal of Biological Chemistry
Volume295
Issue number26
Early online date24 Feb 2020
DOIs
Publication statusPublished - 26 Jun 2020

Keywords

  • O-GlcNAcylation
  • O-GlcNAcase
  • learning
  • habituation
  • Drosophila
  • NMJ
  • O-linked N-acetylglucosamine (O-GlcNAc)
  • neuroscience
  • synapse

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