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Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9–dependent mechanism

The sialomucin endolyn is implicated in adhesion, migration, and differentiation of various cell types. Along rat kidney tubules, endolyn is variously localized to the apical surface and endosomal/lysosomal compartments. Apical delivery of newly synthesized rat endolyn predominates over direct lysos...

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Autores principales: Mo, Di, Costa, Simone A., Ihrke, Gudrun, Youker, Robert T., Pastor-Soler, Nuria, Hughey, Rebecca P., Weisz, Ora A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442411/
https://www.ncbi.nlm.nih.gov/pubmed/22855528
http://dx.doi.org/10.1091/mbc.E12-04-0329
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author Mo, Di
Costa, Simone A.
Ihrke, Gudrun
Youker, Robert T.
Pastor-Soler, Nuria
Hughey, Rebecca P.
Weisz, Ora A.
author_facet Mo, Di
Costa, Simone A.
Ihrke, Gudrun
Youker, Robert T.
Pastor-Soler, Nuria
Hughey, Rebecca P.
Weisz, Ora A.
author_sort Mo, Di
collection PubMed
description The sialomucin endolyn is implicated in adhesion, migration, and differentiation of various cell types. Along rat kidney tubules, endolyn is variously localized to the apical surface and endosomal/lysosomal compartments. Apical delivery of newly synthesized rat endolyn predominates over direct lysosomal delivery in polarized Madin–Darby canine kidney cells. Apical sorting depends on terminal processing of a subset of lumenal N-glycans. Here we dissect the requirements of N-glycan processing for apical targeting and investigate the underlying mechanism. Modulation of glycan branching and subsequent polylactosamine elongation by knockdown of N-acetylglucosaminyltransferase III or V had no effect on apical delivery of endolyn. In contrast, combined but not individual knockdown of sialyltransferases ST3Gal-III, ST3Gal-IV, and ST6Gal-I, which together are responsible for addition of α2,3- and α2,6-linked sialic acids on N-glycans, dramatically decreased endolyn surface polarity. Endolyn synthesized in the presence of kifunensine, which blocks terminal N-glycan processing, reduced its interaction with several recombinant canine galectins, and knockdown of galectin-9 (but not galectin-3, -4, or -8) selectively disrupted endolyn polarity. Our data suggest that sialylation enables recognition of endolyn by galectin-9 to mediate efficient apical sorting. They raise the intriguing possibility that changes in glycosyltransferase expression patterns and/or galectin-9 distribution may acutely modulate endolyn trafficking in the kidney.
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spelling pubmed-34424112012-11-30 Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9–dependent mechanism Mo, Di Costa, Simone A. Ihrke, Gudrun Youker, Robert T. Pastor-Soler, Nuria Hughey, Rebecca P. Weisz, Ora A. Mol Biol Cell Articles The sialomucin endolyn is implicated in adhesion, migration, and differentiation of various cell types. Along rat kidney tubules, endolyn is variously localized to the apical surface and endosomal/lysosomal compartments. Apical delivery of newly synthesized rat endolyn predominates over direct lysosomal delivery in polarized Madin–Darby canine kidney cells. Apical sorting depends on terminal processing of a subset of lumenal N-glycans. Here we dissect the requirements of N-glycan processing for apical targeting and investigate the underlying mechanism. Modulation of glycan branching and subsequent polylactosamine elongation by knockdown of N-acetylglucosaminyltransferase III or V had no effect on apical delivery of endolyn. In contrast, combined but not individual knockdown of sialyltransferases ST3Gal-III, ST3Gal-IV, and ST6Gal-I, which together are responsible for addition of α2,3- and α2,6-linked sialic acids on N-glycans, dramatically decreased endolyn surface polarity. Endolyn synthesized in the presence of kifunensine, which blocks terminal N-glycan processing, reduced its interaction with several recombinant canine galectins, and knockdown of galectin-9 (but not galectin-3, -4, or -8) selectively disrupted endolyn polarity. Our data suggest that sialylation enables recognition of endolyn by galectin-9 to mediate efficient apical sorting. They raise the intriguing possibility that changes in glycosyltransferase expression patterns and/or galectin-9 distribution may acutely modulate endolyn trafficking in the kidney. The American Society for Cell Biology 2012-09-15 /pmc/articles/PMC3442411/ /pubmed/22855528 http://dx.doi.org/10.1091/mbc.E12-04-0329 Text en © 2012 Mo et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Mo, Di
Costa, Simone A.
Ihrke, Gudrun
Youker, Robert T.
Pastor-Soler, Nuria
Hughey, Rebecca P.
Weisz, Ora A.
Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9–dependent mechanism
title Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9–dependent mechanism
title_full Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9–dependent mechanism
title_fullStr Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9–dependent mechanism
title_full_unstemmed Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9–dependent mechanism
title_short Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9–dependent mechanism
title_sort sialylation of n-linked glycans mediates apical delivery of endolyn in mdck cells via a galectin-9–dependent mechanism
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442411/
https://www.ncbi.nlm.nih.gov/pubmed/22855528
http://dx.doi.org/10.1091/mbc.E12-04-0329
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