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

Publication date

2019-11-29

Authors

Muha, Villo
Williamson, Ritchie
Hills, Rachel
McNeilly, Alison D
McWilliams, Thomas G
Alonso, Jana
Schimpl, Marianne
Leney, Aneika C.ISNI 0000000506017505
Heck, AlbertORCID 0000-0002-2405-4404ISNI 0000000393921118
Sutherland, Calum

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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.

Keywords

O-GlcNAcylation, CRMP2, crosstalk, cognitive function

Citation

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', Biology Open, vol. 9, no. 11, 190192. https://doi.org/10.1098/rsob.190192