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Deciphering the functions of O-GlcNAc glycosylation in the brain: The role of site-specific quantitative O-GlcNAcomics

Thompson, John W. and Sorum, Alexander W. and Hsieh-Wilson, Linda C. (2018) Deciphering the functions of O-GlcNAc glycosylation in the brain: The role of site-specific quantitative O-GlcNAcomics. Biochemistry, 57 (27). pp. 4010-4018. ISSN 0006-2960. PMCID PMC6058732. doi:10.1021/acs.biochem.8b00516.

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The dynamic posttranslational modification O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain. Like phosphorylation, O-GlcNAcylation is inducible and plays important functional roles in both physiology and disease. Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins. However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy. Given the sheer number of O-GlcNAc sites, methods for identifying promising sites and prioritizing them for time- and resource-intensive functional studies are greatly needed. Revealing sites that are dynamically altered by different stimuli or disease states will likely go a long way in this regard. Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo. We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites. These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloguing of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins. By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Thompson, John W.0000-0003-0061-4996
Sorum, Alexander W.0000-0003-2526-1445
Hsieh-Wilson, Linda C.0000-0001-5661-1714
Additional Information:© 2018 American Chemical Society. Received: May 4, 2018; Revised: June 22, 2018; Published: June 23, 2018. Special Issue: Molecules and the Brain. This research was supported by the National Institutes of Health (Grants R01GM084724 to L.C.H.-W., T32GM007616 to A.W.S., and T32GM008042, T32GM007616, and F30AG055314 to J.W.T.), the UCLA-Caltech Medical Scientist Training Program (J.W.T.), and the National Science Foundation Graduate Research Fellowship under Grant DGE-1745301 (A.W.S.). The authors declare no competing financial interest.
Funding AgencyGrant Number
NIH Predoctoral FellowshipT32GM007616
NIH Predoctoral FellowshipT32GM008042
NIH Predoctoral FellowshipT32GM007616
NIH Postdoctoral FellowshipF30AG055314
UCLA-Caltech Medical Scientist Training ProgramUNSPECIFIED
NSF Graduate Research FellowshipDGE-1745301
Issue or Number:27
PubMed Central ID:PMC6058732
Record Number:CaltechAUTHORS:20180626-105426484
Persistent URL:
Official Citation:Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of Site-Specific Quantitative O-GlcNAcomics. John W. Thompson, Alexander W. Sorum, and Linda C. Hsieh-Wilson. Biochemistry 2018 57 (27), 4010-4018. DOI: 10.1021/acs.biochem.8b00516
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:87346
Deposited By: Tony Diaz
Deposited On:26 Jun 2018 18:27
Last Modified:09 Mar 2022 18:54

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