Tissue-specific heterogeneity in α-dystroglycan sialoglycosylation: Skeletal muscle α-dystroglycan is a latent receptor for Vicia villosa agglutinin B4 masked by sialic acid modification

James M. Ervasti, Annie L. Burwell, Aimee L. Geissler

Research output: Contribution to journalArticlepeer-review

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Abstract

Because the polypeptide core of α-dystroglycan is encoded by a single gene, the difference in apparent molecular mass between α-dystroglycans expressed in various tissues is presumably due to differential glycosylation. However, little is presently known about the tissue-specific differences in α-dystroglycan glycosylation and whether these modifications may confer functional variability to α-dystroglycan. We recently observed that laminin- 1 binding to skeletal muscle α-dystroglycan was dramatically inhibited by heparin, whereas the binding of commercial merosin to skeletal muscle α- dystroglycan was only marginally inhibited (Pall, E. A., Bolton, K. M., and Ervasti, J. M. (1996) J. Biol. Chem. 3817-3821). In contrast to 156-kDa skeletal muscle α-dystroglycan, both laminin-1 and merosin binding to 120- kDa brain α-dystroglycan were sensitive to heparin. We have now examined the laminin binding properties of 140-kDa α-dystroglycan purified from cardiac muscle and observed that like skeletal muscle α-dystroglycan, heparin inhibited cardiac α-dystroglycan binding to laminin-1, but not to merosin. On the other hand, cardiac and brain α-dystroglycans could be distinguished from skeletal muscle α-dystroglycan by their reactivity with the terminal GalNAc-specific lectin Viola villosa agglutinin. Interestingly, skeletal muscle α-dystroglycan became reactive with V. villosa agglutinin upon digestion with sialidase from Clostridium perfringens, Arthrobacter neurofaciens, or Streptococcus, but not Vibrio cholerae or Newcastle disease virus sialidase. While none of the sialidase treatments affected the laminin binding properties of α-dystroglycan, the sum of our results suggests that skeletal muscle α-dystroglycan contains a novel sialic acid residue linked α2-6 to GalNAc. These properties are also consistent with the cellular characteristics of a GalNAc-terminated glyco-conjugate recently implicated in neuromuscular synap-togenesis. Thus, variations in α-dystroglycan sialoglycosylation may prove as useful markers to further elucidate the role of α-dystroglycan glycoforms in different tissues and perhaps within a single cell type.

Original languageEnglish (US)
Pages (from-to)22315-22321
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number35
DOIs
StatePublished - Aug 29 1997

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