Summary: | Yes === 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. === a Wellcome Trust Senior Research Fellowship (WT087590MA) to D.M.F.v.A., an ARUK Pilot Project grant to R.W., and support from Tenovus Scotland to V.M. The phosphoproteomics mass spectrometry work was supported by the Horizon 2020 program INFRAIA project Epic-XS (project 823839) to A.J.R.H.
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