Tissue-specific heterogeneity in alpha-dystroglycan sialoglycosylation. Skeletal muscle alpha-dystroglycan is a latent receptor for Vicia villosa agglutinin b4 masked by sialic acid modification.
Because the polypeptide core of alpha-dystroglycan is encoded by a single gene, the difference in apparent molecular mass between alpha-dystroglycans expressed in various tissues is presumably due to differential glycosylation. However, little is presently known about the tissue-specific differences in alpha-dystroglycan glycosylation and whether these modifications may confer functional variability to alpha-dystroglycan. We recently observed that laminin-1 binding to skeletal muscle alpha-dystroglycan was dramatically inhibited by heparin, whereas the binding of commercial merosin to skeletal muscle alpha-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 alpha-dystroglycan, both laminin-1 and merosin binding to 120-kDa brain alpha-dystroglycan were sensitive to heparin. We have now examined the laminin binding properties of 140-kDa alpha-dystroglycan purified from cardiac muscle and observed that like skeletal muscle alpha-dystroglycan, heparin inhibited cardiac alpha-dystroglycan binding to laminin-1, but not to merosin. On the other hand, cardiac and brain alpha-dystroglycans could be distinguished from skeletal muscle alpha-dystroglycan by their reactivity with the terminal GalNAc-specific lectin Vicia villosa agglutinin. Interestingly, skeletal muscle alpha-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 alpha-dystroglycan, the sum of our results suggests that skeletal muscle alpha-dystroglycan contains a novel sialic acid residue linked alpha2-6 to GalNAc. These properties are also consistent with the cellular characteristics of a GalNAc-terminated glycoconjugate recently implicated in neuromuscular synaptogenesis. Thus, variations in alpha-dystroglycan sialoglycosylation may prove as useful markers to further elucidate the role of alpha-dystroglycan glycoforms in different tissues and perhaps within a single cell type.
Ervasti
J M
JM
Department of Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. ervasti@facstaff.wisc.edu
Burwell
A L
AL
Geissler
A L
AL
D000818:Animals; D002645:Chickens; D003016:Clostridium perfringens; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D007887:Fabaceae; D006493:Heparin / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D037121:Plant Lectins; D010946:Plants, Medicinal; D011817:Rabbits
D003598:Cytoskeletal Proteins; D007797:Laminin; D037102:Lectins; D008562:Membrane Glycoproteins; D037121:Plant Lectins; C042242:Vicia lectins; D049030:Dystroglycans; D006493:Heparin; D019158:N-Acetylneuraminic Acid