Molecular Recognition by LARGE Is Essential for Expression of Functional Dystroglycan
In: Cell, Jg. 117 (2004-06-25), Heft 7, S. 953-964
academicJournal
Zugriff:
Reduced ligand binding activity of α-dystroglycan is associated with muscle and central nervous system pathogenesis in a growing number of muscular dystrophies. Posttranslational processing of α-dystroglycan is generally accepted to be critical for the expression of functional dystroglycan. Here we show that both the N-terminal domain and a portion of the mucin-like domain of α-dystroglycan are essential for high-affinity laminin-receptor function. Posttranslational modification of α-dystroglycan by glycosyltransferase, LARGE, occurs within the mucin-like domain, but the N-terminal domain interacts with LARGE, defining an intracellular enzyme-substrate recognition motif necessary to initiate functional glycosylation. Gene replacement in dystroglycan-deficient muscle demonstrates that the dystroglycan C-terminal domain is sufficient only for dystrophin-glycoprotein complex assembly, but to prevent muscle degeneration the expression of a functional dystroglycan through LARGE recognition and glycosylation is required. Therefore, molecular recognition of dystroglycan by LARGE is a key determinant in the biosynthetic pathway to produce mature and functional dystroglycan. [Copyright &y& Elsevier]
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Molecular Recognition by LARGE Is Essential for Expression of Functional Dystroglycan
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Autor/in / Beteiligte Person: | Kanagawa, Motoi ; Saito, Fumiaki ; Kunz, Stefan ; Yoshida-Moriguchi, Takako ; Barresi, Rita ; Kobayashi, Yvonne M. ; Muschler, John ; Dumanski, Jan P. ; Michele, Daniel E. ; Oldstone, Michael B.A. ; Campbell, Kevin P. |
Zeitschrift: | Cell, Jg. 117 (2004-06-25), Heft 7, S. 953-964 |
Veröffentlichung: | 2004 |
Medientyp: | academicJournal |
ISSN: | 0092-8674 (print) |
DOI: | 10.1016/j.cell.2004.06.003 |
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