Journal article
Molecular Recognition by LARGE Is Essential for Expression of Functional Dystroglycan
Cell (Cambridge), Vol.117(7), pp.953-964
2004
DOI: 10.1016/j.cell.2004.06.003
PMID: 15210115
Abstract
Reduced ligand binding activity of α-dystroglycan is associated with muscle and central nervous system pathogenesis in a growing number of muscular dystrophies. Posttranslational processing of α-dystroglycan is generally accepted to be critical for the expression of functional dystroglycan. Here we show that both the N-terminal domain and a portion of the mucin-like domain of α-dystroglycan are essential for high-affinity laminin-receptor function. Posttranslational modification of α-dystroglycan by glycosyltransferase, LARGE, occurs within the mucin-like domain, but the N-terminal domain interacts with LARGE, defining an intracellular enzyme-substrate recognition motif necessary to initiate functional glycosylation. Gene replacement in dystroglycan-deficient muscle demonstrates that the dystroglycan C-terminal domain is sufficient only for dystrophin-glycoprotein complex assembly, but to prevent muscle degeneration the expression of a functional dystroglycan through LARGE recognition and glycosylation is required. Therefore, molecular recognition of dystroglycan by LARGE is a key determinant in the biosynthetic pathway to produce mature and functional dystroglycan.
Details
- Title: Subtitle
- Molecular Recognition by LARGE Is Essential for Expression of Functional Dystroglycan
- Creators
- Motoi Kanagawa - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242 USAFumiaki Saito - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242 USAStefan Kunz - The Scripps Research Institute, Division of Virology, Department of Neuropharmacology, La Jolla, CA 92037 USATakako Yoshida-Moriguchi - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242 USARita Barresi - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242 USAYvonne M Kobayashi - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242 USAJohn Muschler - California Pacific Medical Center Research Institute, San Francisco, CA 94115 USAJan P Dumanski - Uppsala University, Department of Genetics and Pathology, Uppsala 751 85, SwedenDaniel E Michele - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242 USAMichael B.A Oldstone - The Scripps Research Institute, Division of Virology, Department of Neuropharmacology, La Jolla, CA 92037 USAKevin P Campbell - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.117(7), pp.953-964
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2004.06.003
- PMID
- 15210115
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 2004
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020775602771
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