Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE.
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.
Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, 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.
Kei-ichiro
K
Inamori
Takako
T
Yoshida-Moriguchi
Yuji
Y
Hara
Mary E
ME
Anderson
Liping
L
Yu
Kevin P
KP
Campbell
D020816:Amino Acid Motifs; D000818:Animals; D016466:CHO Cells; D002236:Carbohydrate Conformation; D020134:Catalytic Domain; D006224:Cricetinae; D049030:Dystroglycans / Q000737:chemistry / Q000378:metabolism*; D020723:Glucuronic Acid / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010430:Pentosyltransferases / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D014994:Xylose / Q000378:metabolism; D000097608:UDP Xylose-Protein Xylosyltransferase
D049030:Dystroglycans; D020723:Glucuronic Acid; D014453:Glucuronosyltransferase; D006025:Glycosaminoglycans; D007797:Laminin; D008024:Ligands; D017351:N-Acetylglucosaminyltransferases; D010430:Pentosyltransferases; D011134:Polysaccharides; D011994:Recombinant Proteins; D014994:Xylose; D000097608:UDP Xylose-Protein Xylosyltransferase; C117674:LARGE1 protein, human; C502747:Large1 protein, mouse