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

Villo Muha; Ritchie Williamson; Rachel Hills; Alison McNeilly; Thomas G. McWilliams; Jana Alonso; Marianne Schimpl; Aneika C. Leney; Albert J. R. Heck; Calum Sutherland; Kevin Read; Rory McCrimmon; Simon P.  Brooks; Daan 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 McNeilly, Thomas G. McWilliams, Jana Alonso, Marianne Schimpl, Aneika C. Leney, Albert J. R. Heck, Calum Sutherland, Kevin Read, Rory McCrimmon, Simon P. Brooks, Daan van Aalten (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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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.

Original language	English
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

CRMP2
O-GlcNAcylation
cognitive function
crosstalk

ASJC Scopus subject areas

General Neuroscience
Immunology
General Biochemistry,Genetics and Molecular Biology

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10.1098/rsob.190192Licence: CC BY

Final Published VersionFinal published version, 1.01 MBLicence: CC BY

Cite this

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

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

note = "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.",

year = "2019",

month = nov,

day = "27",

doi = "10.1098/rsob.190192",

language = "English",

volume = "9",

pages = "1--15",

journal = "Open Biology",

issn = "2046-2441",

publisher = "The Royal Society",

number = "11",

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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

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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 -

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

Abstract

Keywords

ASJC Scopus subject areas

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Molecular Mechanisms of O-GICNAC Signalling (Investigator award)

Aref#d: 20985. Quantitative Analysis of Key Protein Phosphorylation Events Pathway Biomarkers of Metabolic Disease in Human Cells

Sutherland, Calum

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

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Molecular Mechanisms of O-GICNAC Signalling (Investigator award)

Aref#d: 20985. Quantitative Analysis of Key Protein Phosphorylation Events Pathway Biomarkers of Metabolic Disease in Human Cells

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Sutherland, Calum

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