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N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting
Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids. In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammatio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932398/ https://www.ncbi.nlm.nih.gov/pubmed/29755357 http://dx.doi.org/10.3389/fphar.2018.00426 |
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author | Borkham-Kamphorst, Erawan Van de Leur, Eddy Meurer, Steffen K. Buhl, Eva M. Weiskirchen, Ralf |
author_facet | Borkham-Kamphorst, Erawan Van de Leur, Eddy Meurer, Steffen K. Buhl, Eva M. Weiskirchen, Ralf |
author_sort | Borkham-Kamphorst, Erawan |
collection | PubMed |
description | Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids. In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota. Human LCN2 contains one N-glycosylation site conserved in other species. It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion. We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3. Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles. Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding. In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility. |
format | Online Article Text |
id | pubmed-5932398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59323982018-05-11 N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting Borkham-Kamphorst, Erawan Van de Leur, Eddy Meurer, Steffen K. Buhl, Eva M. Weiskirchen, Ralf Front Pharmacol Pharmacology Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids. In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota. Human LCN2 contains one N-glycosylation site conserved in other species. It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion. We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3. Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles. Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding. In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility. Frontiers Media S.A. 2018-04-25 /pmc/articles/PMC5932398/ /pubmed/29755357 http://dx.doi.org/10.3389/fphar.2018.00426 Text en Copyright © 2018 Borkham-Kamphorst, Van de Leur, Meurer, Buhl and Weiskirchen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Borkham-Kamphorst, Erawan Van de Leur, Eddy Meurer, Steffen K. Buhl, Eva M. Weiskirchen, Ralf N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting |
title | N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting |
title_full | N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting |
title_fullStr | N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting |
title_full_unstemmed | N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting |
title_short | N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting |
title_sort | n-glycosylation of lipocalin 2 is not required for secretion or exosome targeting |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932398/ https://www.ncbi.nlm.nih.gov/pubmed/29755357 http://dx.doi.org/10.3389/fphar.2018.00426 |
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