QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online January 12, 2006
doi: 10.1242/10.1242/jcs.02814

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barresi, R. Articles by Campbell, K. P. Search for Related Content PubMed PubMed Citation Articles by Barresi, R. Articles by Campbell, K. P.

Dystroglycan: from biosynthesis to pathogenesis of human disease

Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA

View larger version (17K): [in a new window]   Fig. 1. Dystroglycan domain organization. In the mature -dystroglycan (-DG), the N-terminal domain is cleaved by convertase-like activity between Arg312 and Gln313. Circles indicate O-linked sugar chains. Branches indicate N-linked sugar chains. SP, signal peptide; TM, transmembrane domain; PPXY, dystrophin-binding site. Molecular masses at the bottom refer to the protein mass in the absence (core) and presence of post-translational glycosylation.

View larger version (34K): [in a new window]   Fig. 2. DGC and dystroglycan ligands. Schematic representation of dystroglycan within the DGC. Structural domains of dystroglycan-binding proteins are represented in the insets. Domains of dystrophin described in the text are represented. A similar domain structure is found in utrophin. -Dystrobrevin lacks a WW domain but contains the EF-hand and ZZ domains. Laminins are composed of three distinct chains termed , ß and . To date, 5 , 4 ß and 3 laminin chains have been identified that can combine to form 15 different isoforms (Hallmann et al., 2005). In the C-terminal ends of the chains, there are globular G domains (LG 1-5) composed of five similar modules. Dystroglycan binds with high affinity to the LG domains of laminin 1 (1ß11) and 2 (2ß11) chains (Talts et al., 1999). Antibodies against the C-terminal LG4-LG5 pair of the 1 chain (E3 fragment) have been widely used for organ morphogenesis studies.

View larger version (35K): [in a new window]   Fig. 3. Glycosylation of -dystroglycan. Localization of glycosyltransferases involved in the O-glycosylation pathway of -dystroglycan within the cellular organelles. Known steps of the glycosylation pathway are represented on the left.

View larger version (19K): [in a new window]   Fig. 4. Known and putative glycosyltransferases involved in the O-glycosylation pathway of -dystroglycan. The function of fukutin and FKRP is still unknown. Although it has not been excluded that LARGE and LARGE2 are involved in O-mannosylation of -dystroglycan, it is very likely that overexpression of these putative enzymes stimulates the synthesis of novel and still unknown O-linked sugar chains on the mucin domain of -dystroglycan by direct binding of LARGE to the N-terminal and the first half of the mucin domain.