The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Nitric oxide-dependent processing of heparan sulfate in recycling S-nitrosylated glypican-1 takes place in caveolin-1 containing endosomes.

På svenska

Author

Summary, in English

We have previously demonstrated intracellular degradation of the heparan sulfate side-chains in recycling glypican-1 by heparanase and by deaminative cleavage at N-unsubstituted glucosamine with nitric oxide derived from intrinsic nitrosothiols [see Ding, K., Mani, K., Cheng, F., Belting, M. and Fransson, L.-. (2002) J. Biol. Chem., 277, xxx-xxx; prepub M203383200]. To determine where and in what order events take place, we have visualized, by using confocal laser-scanning immunofluorescence microscopy, glypican-1 variants in unperturbed cells or arrested at various stages of processing. In unperturbed proliferating cells, glypican-1 was partly S-nitrosylated. Intracellular glypican-1 was enriched in endosomes, colocalized significantly with GM-1 ganglioside, caveolin-1 and Rab9-positive endosomes, and carried side-chains rich in N-unsubstituted glucosamine residues. However, such residues were scarce in cell-surface glypican-1. Brefeldin A-arrested glypican-1, which was non-S-nitrosylated and carried side-chains rich in N-unsubstituted glucosamines, colocalized extensively with caveolin-1 but not with Rab9. Suramin, which inhibits heparanase, induced the appearance of S-nitrosylated glypican-1 in caveolin-1-rich compartments. Inhibition of deaminative cleavage did not prevent heparanase from generating heparan sulfate oligosaccharides that colocalized strongly with caveolin-1. Growth-quiescent cells displayed extensive NO-dependent deaminative cleavage of heparan sulfate generating anhydromannose-terminating fragments which were partly associated with acidic vesicles. Proliferating cells generated such fragments during polyamine uptake. We conclude that recycling glypican-1 that is associated with caveolin-1-containing endosomes undergoes sequential N-desulfation/N-deacetylation, heparanase cleavage, S-nitrosylation, NO-release and deaminative cleavage of its side-chains in conjunction with polyamine uptake.

Publishing year

2002

Language

English

Pages

44431-44439

Publication/Series

Journal of Biological Chemistry

Volume

277

Issue

46

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1083-351X