Journal article
The functional O-mannose glycan on α-dystroglycan contains a phospho-ribitol primed for matriglycan addition
eLife, Vol.5, e14473
04/29/2016
DOI: 10.7554/eLife.14473
PMCID: PMC4924997
PMID: 27130732
Abstract
Multiple glycosyltransferases are essential for the proper modification of alpha-dystroglycan, as mutations in the encoding genes cause congenital/limb-girdle muscular dystrophies. Here we elucidate further the structure of an O-mannose-initiated glycan on alpha-dystroglycan that is required to generate its extracellular matrix-binding polysaccharide. This functional glycan contains a novel ribitol structure that links a phosphotrisaccharide to xylose. ISPD is a CDP-ribitol (ribose) pyrophosphorylase that generates the reduced sugar nucleotide for the insertion of ribitol in a phosphodiester linkage to the glycoprotein. TMEM5 is a UDP-xylosyl transferase that elaborates the structure. We demonstrate in a zebrafish model as well as in a human patient that defects in TMEM5 result in muscular dystrophy in combination with abnormal brain development. Thus, we propose a novel structure-a ribitol in a phosphodiester linkage-for the moiety on which TMEM5, B4GAT1, and LARGE act to generate the functional receptor for ECM proteins having LG domains.
Details
- Title: Subtitle
- The functional O-mannose glycan on α-dystroglycan contains a phospho-ribitol primed for matriglycan addition
- Creators
- Jeremy L Praissman - Complex Carbohydrate Research Center, University of Georgia, Athens, United StatesTobias Willer - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, United StatesM Osman Sheikh - Complex Carbohydrate Research Center, University of Georgia, Athens, United StatesAnts Toi - Department of Medical Imaging, Mount Sinai Hospital, Toronto, CanadaDavid Chitayat - Department of Obstetrics and Gynecology, University of Toronto, Toronto, CanadaYung-Yao Lin - Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Hinxton, United KingdomHane Lee - Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United StatesStephanie H Stalnaker - Complex Carbohydrate Research Center, University of Georgia, Athens, United StatesShuo Wang - Complex Carbohydrate Research Center, University of Georgia, Athens, United StatesPradeep Kumar Prabhakar - Complex Carbohydrate Research Center, University of Georgia, Athens, United StatesStanley F Nelson - Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United StatesDerek L Stemple - Wellcome Trust Genome Campus, Wellcome Trust Sanger Institute, Hinxton, United KingdomSteven A Moore - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, United StatesKelley W Moremen - Department of Biochemistry and Molecular Biology, University of Georgia, Athens, United StatesKevin P Campbell - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, United StatesLance Wells - Department of Biochemistry and Molecular Biology, University of Georgia, Athens, United States
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.5, e14473
- DOI
- 10.7554/eLife.14473
- PMID
- 27130732
- PMCID
- PMC4924997
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Publisher
- England
- Grant note
- U54 NS053672 / NINDS NIH HHS P01 GM107012 / NIGMS NIH HHS P41 GM103390 / NIGMS NIH HHS P41 GM103490 / NIGMS NIH HHS RC2 NS069521 / NINDS NIH HHS R01 GM111939 / NIGMS NIH HHS
- Language
- English
- Date published
- 04/29/2016
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984020899202771
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