Subsets of sialylated, sulfated mucins of diverse origins are recognized by L-selectin. Lack of evidence for unique oligosaccharide sequences mediating binding

被引:50
作者
Crottet, P
Kim, YJ
Varki, A
机构
[1] UNIV CALIF SAN DIEGO,CTR CANC,GLYCOBIOL PROGRAM,LA JOLLA,CA 92093
[2] UNIV CALIF SAN DIEGO,DIV CELLULAR & MOLEC MED,LA JOLLA,CA 92093
关键词
L-selectin; mucins; sialic acid; sulfate; adhesion;
D O I
10.1093/glycob/6.2.191
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have shown that the mucin-type polypeptides GlyCAM-1, CD34, and MAdCAM-1 can function as ligands for L-selectin only when they are synthesized by the specialized high-endothelial venules (HEV) of lymph nodes, Since sialylation, sulfation, and possibly fucosylation are required for generating recognition, we reasoned that other mucins known to have such components might also bind L-selectin. We show here that soluble mucins secreted by human colon carcinoma cells, as well as those derived from human bronchial mucus can bind to human L-selectin in a calcium-dependent manner. As with GlyCAM-1 synthesized by lymph node HEV, alpha 2-3 linked sialic acids and sulfation seem to play a critical role in generating this L-selectin binding, In each case, only a subset of the mucin molecules is recognized by L-selectin, Binding is not destroyed by boiling, suggesting that recognition may bei based primarily upon carbohydrate structures, Despite this, O-linked oligosaccharide chains released from these ligands by beta-elimination do not show any detectable binding to L-selectin, Following protease treatment of the ligands, binding persists in a subset of the resulting fragments, indicating that specific recognition is determined by certain regions of the original mucins, However, O-linked oligosaccharides released from the subset of non-binding mucin fragments do not show very different size and charge profiles compared to those that do bind, Furthermore, studies with polylactosamine-degrading endoglycosidases suggest that the core structures involved in generating binding can vary among the different ligands. Taken together, these data indicate that a single unique oligosaccharide structure may not be responsible for high-affinity binding. Rather, diverse mucins with sialylated, sulfated, fucosylated lactosamine-type O-linked oligosaccharides can generate high-affinity L-selectin ligands, but only when they present these chains in unique spacing and/or clustered combinations, presumably dictated by the polypeptide backbone.
引用
收藏
页码:191 / 208
页数:18
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