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

Villo Muha; Ritchie Williamson; Rachel Hills; Alison D. McNeilly; Thomas G. McWilliams; Jana Alonso; Marianne Schimpl; Aneika C. Leney; Albert J.R. Heck; Calum Sutherland; Kevin D. Read; Rory J. McCrimmon; Simon P. Brooks; Daan M.F. Van Aalten

doi:10.1098/rsob.190192

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

Villo Muha
, Ritchie Williamson
, Rachel Hills
, Alison D. McNeilly
, Thomas G. McWilliams
, Jana Alonso
, Marianne Schimpl
, Aneika C. Leney
, Albert J.R. Heck
, Calum Sutherland
, Kevin D. Read
, Rory J. McCrimmon
, Simon P. Brooks
, Daan M.F. Van Aalten^*

^*Corresponding author for this work

Biosciences

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

211 Downloads (Pure)

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 Crmp2^S517A 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 language	English
Article number	190192
Pages (from-to)	1-15
Number of pages	15
Journal	Open Biology
Volume	9
Issue number	11
DOIs	https://doi.org/10.1098/rsob.190192
Publication status	Published - 27 Nov 2019

Keywords

cognitive function
CRMP2
crosstalk
O-GlcNAcylation

ASJC Scopus subject areas

General Neuroscience
Immunology
General Biochemistry,Genetics and Molecular Biology

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Muha, V., Williamson, R., Hills, R., McNeilly, A. D., McWilliams, T. G., Alonso, J., Schimpl, M., Leney, A. C., Heck, A. J. R., Sutherland, C., Read, K. D., McCrimmon, R. J., Brooks, S. P., & Van Aalten, D. M. F. (2019). Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice. Open Biology, 9(11), 1-15. Article 190192. https://doi.org/10.1098/rsob.190192

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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.",

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AU - McWilliams, Thomas G.

AU - Alonso, Jana

AU - Schimpl, Marianne

AU - Leney, Aneika C.

AU - Heck, Albert J.R.

AU - Sutherland, Calum

AU - Read, Kevin D.

AU - McCrimmon, Rory J.

AU - Brooks, Simon P.

AU - Van Aalten, Daan M.F.

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AB - 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.

KW - cognitive function

KW - CRMP2

KW - crosstalk

KW - O-GlcNAcylation

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JF - Open Biology

IS - 11

M1 - 190192

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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