Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice

Open Biol. 2019 Nov 29;9(11):190192. doi: 10.1098/rsob.190192. Epub 2019 Nov 27.

Abstract

O-GlcNAcylation is an abundant post-translational modification in the nervous system, linked to both neurodevelopmental and neurodegenerative disease. However, the mechanistic links between these phenotypes and site-specific O-GlcNAcylation remain largely unexplored. Here, we show that Ser517 O-GlcNAcylation of the microtubule-binding protein Collapsin Response Mediator Protein-2 (CRMP2) increases with age. By generating and characterizing a Crmp2S517A knock-in mouse model, we demonstrate that loss of O-GlcNAcylation leads to a small decrease in body weight and mild memory impairment, suggesting that Ser517 O-GlcNAcylation has a small but detectable impact on mouse physiology and cognitive function.

Keywords: CRMP2; O-GlcNAcylation; cognitive function; crosstalk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / analysis
  • Acetylglucosamine / metabolism*
  • Aging
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cognition*
  • Exploratory Behavior
  • Female
  • Gene Knock-In Techniques
  • Humans
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Memory Disorders / genetics
  • Memory Disorders / metabolism
  • Memory, Short-Term*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Point Mutation
  • Protein Processing, Post-Translational

Substances

  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • collapsin response mediator protein-2
  • Acetylglucosamine