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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.

SUBMITTER: Muha V

PROVIDER: S-EPMC6893399 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Muha Villo V Williamson Ritchie R Hills Rachel R McNeilly Alison D AD McWilliams Thomas G TG Alonso Jana J Schimpl Marianne M Leney Aneika C AC Heck Albert J R AJR Sutherland Calum C Read Kevin D KD McCrimmon Rory J RJ Brooks Simon P SP van Aalten Daan M F DMF

Open biology 20191127 11

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 <i>Crmp2<sup>S517A</sup></i> knock-in mouse model, we ...[more]

PMID: 31771416

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

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