Journal article
O-Mannosyl Phosphorylation of Alpha-Dystroglycan is Required for Laminin Binding
Science (American Association for the Advancement of Science), Vol.327(5961), pp.88-92
01/01/2010
DOI: 10.1126/science.1180512
PMID: 20044576
Abstract
Alpha-dystroglycan is a cell-surface glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains and certain arenaviruses. Receptor binding is thought to be mediated by a post-translational modification, and defective binding with laminin underlies a subclass of congenital muscular dystrophy. Here, using mass spectrometry- and NMR-based structural analyses, we identified a phosphorylated
O
-mannosyl glycan on the mucin-like domain of recombinant alpha-dystroglycan, which was required for laminin binding. We demonstrated that patients with muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, as well as mice with myodystrophy, commonly have defects in a post-phosphoryl modification of this phosphorylated
O
-linked mannose, and that this modification is mediated by the like-acetylglucosaminyltransferase (LARGE) protein. Our findings expand our understanding of the mechanisms that underlie congenital muscular dystrophy.
Details
- Title: Subtitle
- O-Mannosyl Phosphorylation of Alpha-Dystroglycan is Required for Laminin Binding
- Creators
- Takako Yoshida-Moriguchi - Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, Iowa 52242-1101, USALiping Yu - Medical NMR Facility, University of Iowa Roy J. and Lucille A. Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, Iowa 52242-1101, USAStephanie H Stalnaker - Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Rd., Athens, Georgia 30602, USASarah Davis - Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, Iowa 52242-1101, USAStefan Kunz - Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, SwitzerlandMichael B.A Oldstone - Scripps Research Institute, Department of Immunology and Microbial Science, 10550 N. Torrey Pines Road, La Jolla, CA 92037Harry Schachter - Hospital for Sick Children, Toronto, Ontario M5G 1X8, CanadaLance Wells - Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Rd., Athens, Georgia 30602, USAKevin P Campbell - Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, Iowa 52242-1101, USA
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.327(5961), pp.88-92
- DOI
- 10.1126/science.1180512
- PMID
- 20044576
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Language
- English
- Date published
- 01/01/2010
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology; Medicine Administration
- Record Identifier
- 9984020737302771
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