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

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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 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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title = "Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice",

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 = "cognitive function, CRMP2, crosstalk, O-GlcNAcylation",

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

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AU - Muha, Villo

AU - Williamson, Ritchie

AU - Hills, Rachel

AU - McNeilly, Alison D.

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.

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KW - CRMP2

KW - crosstalk

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

Abstract

Keywords

ASJC Scopus subject areas

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