Journal article
Glycomic Analyses of Mouse Models of Congenital Muscular Dystrophy
The Journal of biological chemistry, Vol.286(24), pp.21180-21190
06/17/2011
DOI: 10.1074/jbc.M110.203281
PMCID: PMC3122180
PMID: 21460210
Abstract
Dystroglycanopathies are a subset of congenital muscular dystrophies wherein α-dystroglycan (α-DG) is hypoglycosylated. α-DG is an extensively
O
-glycosylated extracellular matrix-binding protein and a key component of the dystrophin-glycoprotein complex. Previous studies have shown α-DG to be post-translationally modified by both
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-GalNAc- and
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-mannose-initiated glycan structures. Mutations in defined or putative glycosyltransferase genes involved in
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-mannosylation are associated with a loss of ligand-binding activity of α-DG and are causal for various forms of congenital muscular dystrophy. In this study, we sought to perform glycomic analysis on brain
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-linked glycan structures released from proteins of three different knock-out mouse models associated with
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-mannosylation (POMGnT1, LARGE (Myd), and DAG1
−/−
). Using mass spectrometry approaches, we were able to identify nine
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-mannose-initiated and 25
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-GalNAc-initiated glycan structures in wild-type littermate control mouse brains. Through our analysis, we were able to confirm that POMGnT1 is essential for the extension of all observed
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-mannose glycan structures with β1,2-linked GlcNAc. Loss of LARGE expression in the Myd mouse had no observable effect on the
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-mannose-initiated glycan structures characterized here. Interestingly, we also determined that similar amounts of
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-mannose-initiated glycan structures are present on brain proteins from α-DG-lacking mice (DAG1) compared with wild-type mice, indicating that there must be additional proteins that are
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-mannosylated in the mammalian brain. Our findings illustrate that classical β1,2-elongation and β1,6-GlcNAc branching of
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-mannose glycan structures are dependent upon the POMGnT1 enzyme and that
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-mannosylation is not limited solely to α-DG in the brain.
Details
- Title: Subtitle
- Glycomic Analyses of Mouse Models of Congenital Muscular Dystrophy
- Creators
- Stephanie H Stalnaker - From theKazuhiro Aoki - From theJae-Min Lim - From theMindy Porterfield - From theMian Liu - From theJakob S Satz - theSean Buskirk - From theYufang Xiong - thePeng Zhang - theKevin P Campbell - theHuaiyu Hu - theDavid Live - From theMichael Tiemeyer - From theLance Wells - From the
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.286(24), pp.21180-21190
- DOI
- 10.1074/jbc.M110.203281
- PMID
- 21460210
- PMCID
- PMC3122180
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- HD060458; NS066582 / National Institutes of Health
- Alternative title
- O-Linked Glycans of Mouse Models of CMD
- Language
- English
- Date published
- 06/17/2011
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020878102771
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