Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha-Dystroglycan is a heavily glycosylated protein, which is localized on the Schwann cell membrane as well as the sarcolemma, and links the transmembrane protein beta-dystroglycan to laminin in the extracellular matrix. We have shown previously that sialidase treatment, but not N-glycanase treatment, of bovine peripheral nerve alpha-dystroglycan greatly reduces its binding activity to laminin, suggesting that the sialic acid of O-glycosidically-linked oligosaccharides may be essential for this binding. In this report, we analyzed the structures of the sialylated O-linked oligosaccharides of bovine peripheral nerve alpha-dystroglycan by two methods. O-Glycosidically-linked oligosaccharides were liberated by alkaline-borotritide treatment or by mild hydrazinolysis followed by 2-aminobenzamide-derivatization. Acidic fractions obtained by anion exchange column chromatography that eluted at a position corresponding to monosialylated oligosaccharides were converted to neutral oligosaccharides by exhaustive sialidase digestion. The sialidases from Arthrobacter ureafaciens and from Newcastle disease virus resulted in the same degree of hydrolysis. The neutral oligosaccharide fraction, thus obtained, gave a major peak with a mobility of 3.8-3.9 glucose units upon gel filtration, and its reducing terminus was identified as a mannose derivative. Based on the results of sequential exoglycosidase digestion, lectin column chromatography, and reversed-phase high-performance liquid chromatography, we concluded that the major sialylated O-glycosidically-linked oligosaccharide of the alpha-dystroglycan was a novel O-mannosyl-type oligosaccharide, the structure of which was Siaalpha2-3Galbeta1-4GlcNAcbeta1-2Man-Ser/Thr (where Sia is sialic acid). This oligosaccharide constituted at least 66% of the sialylated O-linked sugar chains. Furthermore, a laminin binding inhibition study suggested that the sialyl N-acetyllactosamine moiety of this sugar chain was involved in the interaction of the alpha-dystroglycan with laminin.
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PMID:Structures of sialylated O-linked oligosaccharides of bovine peripheral nerve alpha-dystroglycan. The role of a novel O-mannosyl-type oligosaccharide in the binding of alpha-dystroglycan with laminin. 899 17

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.
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PMID: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. 926 82

Distal myopathy with rimmed vacuoles (DMRV), is an autosomal recessive disorder with early adult onset, displays distal dominant muscular involvement and is characterized by the presence of numerous rimmed vacuoles in the affected muscle fibers. The pathophysiology of DMRV has not been clarified yet, although the responsible gene was identified as that encoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase involved in the biosynthesis of sialic acids. To identify defective carbohydrate moieties of muscular glycoproteins from DMRV patients, frozen skeletal muscle sections from seven patients with DMRV, as well as normal and pathological controls, were treated with or without sialidase or N-glycosidase F followed by lectin staining and lectin blotting analysis. The sialic acid contents of the O-glycans in the skeletal muscle specimens from the DMRV patients were also measured. We found that Arachis hypogaea agglutinin (PNA) lectin reacted strongly with sarcolemmal glycoproteins in the DMRV patients but not with those in control subjects. alpha-Dystroglycan from the DMRV patients strongly associated with PNA lectin, although that from controls did not. The sialic acid level of the O-glycans in the DMRV muscular glycoproteins with molecular weights of 30 to 200 kd was reduced to 60 to 80% of the control level. The results show that impaired sialyl O-glycan formation in muscular glycoproteins, including alpha-dystroglycan, occurs in DMRV.
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PMID:Distal myopathy with rimmed vacuoles: impaired O-glycan formation in muscular glycoproteins. 1579 92

Carbohydrate modifications are clearly important to the function of alpha-dystroglycan but their composition and structure remain poorly understood. In the present study, we describe experiments aimed at identifying the alpha-dystroglycan oligosaccharides important for its binding to laminin-1 and carbohydrate-dependent mAbs (monoclonal antibodies) IIH6 and VIA4(1). We digested highly purified skeletal muscle alpha-dystroglycan with an array of linkage-specific endo- and exoglycosidases, which were verified for action on alpha-dystroglycan by loss/gain of reactivity for lectins with defined glyco-epitopes. Notably, digestion with a combination of Arthrobacter ureafaciens sialidase, beta(1-4)galactosidase and beta-N-acetylglucosaminidase substantially degraded SiaAalpha2-3Galbeta1-4GlcNAcbeta1-2Man glycans on highly purified alpha-dystroglycan that nonetheless exhibited enhanced IIH6, VIA4(1) and laminin-1 binding activity. Additional results indicate that alpha-dystroglycan is probably modified with other anionic sugars besides sialic acid and suggest that rare alpha-linked GlcNAc moieties may block its complete deglycosylation with currently available enzymes.
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PMID:Enhanced laminin binding by alpha-dystroglycan after enzymatic deglycosylation. 1586 2