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

Villo Muha, Ritchie Williamson, Rachel Hills, Alison McNeilly, Thomas G. McWilliams, Jana Alonso, Marianne Schimpl, Aneika C. Leney, Albert J. R. Heck, Calum Sutherland, Kevin Read, Rory McCrimmon, Simon P. Brooks, Daan van Aalten (Lead / Corresponding author)

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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.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalOpen Biology
Volume9
Issue number11
DOIs
Publication statusPublished - 27 Nov 2019

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Neurodegenerative diseases
Physiology
Object recognition
Neurology
Carrier Proteins
Microtubule Proteins
Data storage equipment
Post Translational Protein Processing
Neurodegenerative Diseases
Cognition
Nervous System
Body Weight
Phenotype
collapsin response mediator protein-2
Recognition (Psychology)

Keywords

  • CRMP2
  • O-GlcNAcylation
  • cognitive function
  • crosstalk

Cite this

Muha, Villo ; Williamson, Ritchie ; Hills, Rachel ; McNeilly, Alison ; McWilliams, Thomas G. ; Alonso, Jana ; Schimpl, Marianne ; Leney, Aneika C. ; Heck, Albert J. R. ; Sutherland, Calum ; Read, Kevin ; McCrimmon, Rory ; Brooks, Simon P. ; van Aalten, Daan. / Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice. In: Open Biology. 2019 ; Vol. 9, No. 11. pp. 1-15.
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Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice. / Muha, Villo; Williamson, Ritchie; Hills, Rachel; McNeilly, Alison; McWilliams, Thomas G.; Alonso, Jana; Schimpl, Marianne; Leney, Aneika C.; Heck, Albert J. R.; Sutherland, Calum; Read, Kevin; McCrimmon, Rory; Brooks, Simon P. ; van Aalten, Daan (Lead / Corresponding author).

In: Open Biology, Vol. 9, No. 11, 27.11.2019, p. 1-15.

Research output: Contribution to journalArticle

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AU - Williamson, Ritchie

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AU - McWilliams, Thomas G.

AU - Alonso, Jana

AU - Schimpl, Marianne

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AU - Heck, Albert J. R.

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AU - Read, Kevin

AU - McCrimmon, Rory

AU - Brooks, Simon P.

AU - van Aalten, Daan

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