Journal article
Xylosyl- and glucuronyltransferase functions of LARGE in α-dystroglycan modification are conserved in LARGE2
Glycobiology (Oxford), Vol.23(3), pp.295-302
03/2013
DOI: 10.1093/glycob/cws152
PMCID: PMC3555503
PMID: 23125099
Abstract
LARGE-dependent modification enables α-dystroglycan (α-DG) to bind to its extracellular matrix ligands. Mutations in the
LARGE
gene and several others involved in
O
-mannosyl glycan synthesis have been identified in congenital and limb-girdle muscular dystrophies that are characterized by perturbed glycosylation and reduced ligand-binding affinity of α-DG. LARGE is a bifunctional glycosyltransferase that alternately transfers xylose and glucuronic acid, thereby generating the heteropolysaccharides on α-DG that confer its ligand binding. Although the LARGE paralog LARGE2 (also referred to as GYLTL1B) has likewise been shown to enhance the functional modification of α-DG in cultured cells, its enzymatic activities have not been identified. Here, we report that LARGE2 is also a bifunctional glycosyltransferase and compare its properties with those of LARGE. By means of a high-performance liquid chromatography-based enzymatic assay, we demonstrate that like LARGE, LARGE2 has xylosyltransferase (Xyl-T) and glucuronyltransferase (GlcA-T) activities, as well as polymerizing activity. Notably, however, the pH optima of the Xyl-T and GlcA-T of LARGE2 are distinct from one another and also from those of LARGE. Our results suggest that LARGE and LARGE2 catalyze the same glycosylation reactions for the functional modification of α-DG, but that they have different biochemical properties.
Details
- Title: Subtitle
- Xylosyl- and glucuronyltransferase functions of LARGE in α-dystroglycan modification are conserved in LARGE2
- Creators
- Kei-ichiro Inamori - University of Iowa Roy J. and Lucille A. Carver College of MedicineYuji Hara - University of Iowa Roy J. and Lucille A. Carver College of MedicineTobias Willer - University of Iowa Roy J. and Lucille A. Carver College of MedicineMary E Anderson - University of Iowa Roy J. and Lucille A. Carver College of MedicineZihan Zhu - University of Iowa Roy J. and Lucille A. Carver College of MedicineTakako Yoshida-Moriguchi - University of Iowa Roy J. and Lucille A. Carver College of MedicineKevin P Campbell - University of Iowa Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Glycobiology (Oxford), Vol.23(3), pp.295-302
- DOI
- 10.1093/glycob/cws152
- PMID
- 23125099
- PMCID
- PMC3555503
- NLM abbreviation
- Glycobiology
- ISSN
- 0959-6658
- eISSN
- 1460-2423
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 03/2013
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020727702771
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