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Science 335 (6064): 93-96

Copyright © 2012 by the American Association for the Advancement of Science

Dystroglycan Function Requires Xylosyl- and Glucuronyltransferase Activities of LARGE

Kei-ichiro Inamori,1,* Takako Yoshida-Moriguchi,1,* Yuji Hara,1 Mary E. Anderson,1 Liping Yu,2 Kevin P. Campbell1,{dagger}

Abstract: Posttranslational modification of alpha-dystroglycan (α-DG) by the like-acetylglucosaminyltransferase (LARGE) is required for it to function as an extracellular matrix (ECM) receptor. Mutations in the LARGE gene have been identified in congenital muscular dystrophy patients with brain abnormalities. However, the precise function of LARGE remains unclear. Here we found that LARGE could act as a bifunctional glycosyltransferase, with both xylosyltransferase and glucuronyltransferase activities, which produced repeating units of [–3-xylose–α1,3-glucuronic acid-β1–]. This modification allowed α-DG to bind laminin-G domain–containing ECM ligands.

1 Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, Department of Neurology, Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, 4283 Carver Biomedical Research Building, 285 Newton Road, Iowa City, IA 52242–1101, USA.
2 Medical Nuclear Magnetic Resonance Facility, University of Iowa Roy J. and Lucille A. Carver College of Medicine, B291 Carver Biomedical Research Building, 285 Newton Road, Iowa City, IA 52242–1101, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: kevin-campbell{at}uiowa.edu


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