N-Glycosylation affects the stability and barrier function of the MUC16 mucin
| Autor: | Sylvain Lehoux, Pablo Argüeso, Nicole M. McColgan, Takazumi Taniguchi, Jerome Mauris, Sarah Melissa P. Jacobo, Ashley M. Woodward, Paula Magnelli |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Mucin Glycobiology and Extracellular Matrices Cell Biology Tunicamycin Golgi apparatus Biology Biochemistry Transmembrane protein Cell biology Glycocalyx 03 medical and health sciences chemistry.chemical_compound symbols.namesake 030104 developmental biology 0302 clinical medicine chemistry 030220 oncology & carcinogenesis symbols Glycoprotein Molecular Biology Barrier function Galectin |
| Zdroj: | Journal of Biological Chemistry. 292:11079-11090 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m116.770123 |
| Popis: | Transmembrane mucins are highly O-glycosylated glycoproteins that coat the apical glycocalyx on mucosal surfaces and represent the first line of cellular defense against infection and injury. Relatively low levels of N-glycans are found on transmembrane mucins, and their structure and function remain poorly characterized. We previously reported that carbohydrate-dependent interactions of transmembrane mucins with galectin-3 contribute to maintenance of the epithelial barrier at the ocular surface. Now, using MALDI-TOF mass spectrometry, we report that transmembrane mucin N-glycans in differentiated human corneal epithelial cells contain primarily complex-type structures with N-acetyllactosamine, a preferred galectin ligand. In N-glycosylation inhibition experiments, we find that treatment with tunicamycin and siRNA-mediated knockdown of the Golgi N-acetylglucosaminyltransferase I gene (MGAT1) induce partial loss of both total and cell-surface levels of the largest mucin, MUC16, and a concomitant reduction in glycocalyx barrier function. Moreover, we identified a distinct role for N-glycans in promoting MUC16's binding affinity toward galectin-3 and in causing retention of the lectin on the epithelial cell surface. Taken together, these studies define a role for N-linked oligosaccharides in supporting the stability and function of transmembrane mucins on mucosal surfaces. |
| Databáze: | OpenAIRE |
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