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

TY - JOUR

T1 - Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice

AU - Muha, Villo

AU - Williamson, Ritchie

AU - Hills, Rachel

AU - McNeilly, Alison

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

AU - McCrimmon, Rory

AU - Brooks, Simon P.

AU - van Aalten, Daan

N1 - This work was funded by 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.

PY - 2019/11/27

Y1 - 2019/11/27

N2 - 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.

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 - CRMP2

KW - O-GlcNAcylation

KW - cognitive function

KW - crosstalk

UR - https://www.scopus.com/pages/publications/85075658823

U2 - 10.1098/rsob.190192

DO - 10.1098/rsob.190192

M3 - Article

C2 - 31771416

SN - 2046-2441

VL - 9

SP - 1

EP - 15

JO - Open Biology

JF - Open Biology

IS - 11

ER -