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Molecular recognition by large is essential for expression of functional dystroglycan

Academic Article
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Overview

authors

  • Kanagawa, M.
  • Saito, F.
  • Kunz, S.
  • Yoshida-Moriguchi, T.
  • Barresi, R.
  • Kobayashi, Y. M.
  • Muschler, J.
  • Dumanski, J. P.
  • Michele, D. E.
  • Oldstone, Michael
  • Campbell, K. P.

publication date

  • 2004

journal

  • Cell  Journal

abstract

  • Reduced ligand binding activity of alpha-dystroglycan is associated with muscle and central nervous system pathogenesis in a growing number of muscular dystrophies. Posttranslational processing of alpha-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 alpha-dystroglycan are essential for high-affinity laminin-receptor function. Posttranslational modification of alpha-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.

subject areas

  • Adenoviridae
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Dystroglycans
  • Glycosylation
  • Glycosyltransferases
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Rabbits
  • Receptors, Laminin
  • Recombinant Fusion Proteins
  • Stem Cells
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Identity

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2004.06.003

PubMed ID

  • 15210115
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Additional Document Info

start page

  • 953

end page

  • 964

volume

  • 117

issue

  • 7

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