Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317/319 is required for laminin binding and arenavirus infection.

Détails

ID Serval
serval:BIB_9244AE85D5D1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317/319 is required for laminin binding and arenavirus infection.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Hara Y., Kanagawa M., Kunz S., Yoshida-Moriguchi T., Satz J.S., Kobayashi Y.M., Zhu Z., Burden S.J., Oldstone M.B., Campbell K.P.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2011
Volume
108
Numéro
42
Pages
17426-17431
Langue
anglais
Résumé
α-dystroglycan is a highly O-glycosylated extracellular matrix receptor that is required for anchoring of the basement membrane to the cell surface and for the entry of Old World arenaviruses into cells. Like-acetylglucosaminyltransferase (LARGE) is a key molecule that binds to the N-terminal domain of α-dystroglycan and attaches ligand-binding moieties to phosphorylated O-mannose on α-dystroglycan. Here we show that the LARGE modification required for laminin- and virus-binding occurs on specific Thr residues located at the extreme N terminus of the mucin-like domain of α-dystroglycan. Deletion and mutation analyses demonstrate that the ligand-binding activity of α-dystroglycan is conferred primarily by LARGE modification at Thr-317 and -319, within the highly conserved first 18 amino acids of the mucin-like domain. The importance of these paired residues in laminin-binding and clustering activity on myoblasts and in arenavirus cell entry is confirmed by mutational analysis with full-length dystroglycan. We further demonstrate that a sequence of five amino acids, Thr(317)ProThr(319)ProVal, contains phosphorylated O-glycosylation and, when modified by LARGE is sufficient for laminin-binding. Because the N-terminal region adjacent to the paired Thr residues is removed during posttranslational maturation of dystroglycan, our results demonstrate that the ligand-binding activity resides at the extreme N terminus of mature α-dystroglycan and is crucial for α-dystroglycan to coordinate the assembly of extracellular matrix proteins and to bind arenaviruses on the cell surface.
Pubmed
Web of science
Création de la notice
10/11/2011 11:48
Dernière modification de la notice
03/03/2018 19:31
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