Like-Glycosyltransferase; Glycosyltransferase-Like 1B (LARGE, GYLTL1B)

  • Kei-ichiro Inamori
  • Kevin P. Campbell
Reference work entry


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).


Muscular Dystrophy Functional Modification Congenital Muscular Dystrophy Lassa Fever Laminin Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Division of GlycopathologyInstitute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical UniversitySendaiJapan
  2. 2.Howard Hughes Medical Institute, Department of Molecular Physiology and BiophysicsUniversity of Iowa Roy J. and Lucille A. Carver College of MedicineIowa CityUSA

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