Book chapter
Like-Glycosyltransferase; Glycosyltransferase-Like 1B (LARGE, GYLTL1B)
Handbook of Glycosyltransferases and Related Genes, pp.1167-1179
Springer Japan
02/05/2014
DOI: 10.1007/978-4-431-54240-7_60
Abstract
The like-acetylglucosaminyltransferase (LARGE) gene was originally identified and cloned from a region on human chromosome 22 that is frequently deleted in meningiomas (Peyrard et al. 1999). In 2001, a spontaneous mutation in the mouse ortholog was identified in the myodystrophy (myd) mouse, and α-dystroglycan (α-DG) was found to be hypoglycosylated (Grewal et al. 2001). α-DG is highly decorated with O-glycans, and the LARGE-dependent modification of a particular O-mannosyl glycan on α-DG is essential for its binding to various extracellular matrix ligands such as laminin, perlecan, agrin, and neurexin (Barresi and Campbell 2006). Notably, the same α-DG modification is required for the binding and entry of lymphocytic choriomeningitis virus and Lassa fever virus (Cao et al. 1998). Reduced ligand binding by α-DG due to defective glycosylation is a common pathogenic feature of dystroglycanopathies – congenital muscular dystrophies (CMDs) that are often accompanied by brain and eye abnormalities and limb-girdle muscular dystrophies (Barresi and Campbell 2006; Godfrey et al. 2011). Mutations in the genes encoding LARGE (Longman et al. 2003) and other proteins involved in O-mannosyl glycan synthesis – including protein O-mannosyltransferase 1 (POMT1) (Beltran-Valero de Bernabe et al. 2002), POMT2 (van Reeuwijk et al. 2005), protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) (Yoshida et al. 2001), fukutin (Kobayashi et al. 1998), and fukutin-related protein (FKRP) (Brockington et al. 2001) – have been identified in these disorders. Recently, LARGE was found to be a bifunctional glycosyltransferase that has xylosyltransferase (Xyl-T) and glucuronyltransferase (GlcA-T) activities, which are required for the receptor function of α-DG (Inamori et al. 2012).
Details
- Title: Subtitle
- Like-Glycosyltransferase; Glycosyltransferase-Like 1B (LARGE, GYLTL1B)
- Creators
- Kei-ichiro Inamori - Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, JapanKevin P Campbell - Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, USA
- Resource Type
- Book chapter
- Publication Details
- Handbook of Glycosyltransferases and Related Genes, pp.1167-1179
- DOI
- 10.1007/978-4-431-54240-7_60
- Publisher
- Springer Japan; Tokyo
- Language
- English
- Date published
- 02/05/2014
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984068369702771
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