A switch of N-glycosylation of proteome and secretome during differentiation of intestinal epithelial cells

Paweł Link-Lenczowski , Martyna Jastrzębska , Katarzyna Chwalenia , Małgorzata Pierzchalska , Anna Leja-Szpak , Joanna Bonior , Piotr Pierzchalski , Jolanta Jaworek


The maintenance of homeostasis of the intestinal epithelium depends on the complex process of epithelial cells differentiation, which repeatedly continues throughout the entire life. Many studies suggest, that cellular differentiation is regulated by glycosylation, or at least that changes of the latter are the hallmark of the process. The detailed description and understanding of this relationship are important in the context of gastrointestinal tract disease, including cancer. Here we employ a broadly used in vitro model of intestinal cell differentiation to track the glycosylation changes in details. We analyzed the glycoproteome- and glycosecretome-derived N-glycomes of undifferentiated Caco-2 adenocarcinoma cells and Caco-2-derived enterocyte-like cells. We used HILIC-HPLC and MALDI-ToF-MS approach together with exoglycosidases digestions to describe qualitative and quantitative N-glycosylation changes upon differentiation. Derived glycan traits analysis revealed, that differentiation results in substantial upregulation of sialylation of glycoproteome and increment of fucosylation within glycosecretome. This was also clearly visible when we analyzed the abundances of individual glycan species. Moreover, we observed the characteristic shift within oligomannose N-glycans, suggesting the augmentation of mannose trimming, resulting in downregulation of H8N2 and upregulation of H5N2 glycan. This was supported by elevated expression of Golgi alpha-mannosidases (especially MAN1C1). We hypothesize, that intensified mannose trimming at the initial steps of N-glycosylation pathway during differentiation, together with the remodeling of the expression of key glycosyltransferases leads to increased diversity of N-glycans and enhanced fucosylation and sialylation of complex structures. Finally, we propose H4N5F1 glycan as a potential biomarker of intestinal epithelial cell differentiation.
Author Paweł Link-Lenczowski
Paweł Link-Lenczowski,,
, Martyna Jastrzębska
Martyna Jastrzębska,,
, Katarzyna Chwalenia
Katarzyna Chwalenia,,
, Małgorzata Pierzchalska (FoFT / DoFB)
Małgorzata Pierzchalska,,
- Department of Food Biotechnology
, Anna Leja-Szpak
Anna Leja-Szpak,,
, Joanna Bonior
Joanna Bonior,,
, Piotr Pierzchalski
Piotr Pierzchalski,,
, Jolanta Jaworek
Jolanta Jaworek,,
Journal seriesBiochimica et Biophysica Acta-Molecular Cell Research, [Biochimica et Biophysica Acta - Molecular Cell Research], ISSN 0167-4889, (N/A 140 pkt)
Issue year2019
Publication size in sheets0.65
Article number118555
Keywords in EnglishColon adenocarcinoma, Enterocyte, Glycosylation, Glycome, Secretome, Differentiation
ASJC Classification1307 Cell Biology; 1312 Molecular Biology
URL https://www.sciencedirect.com/science/article/pii/S0167488919301661/pdfft?md5=615354547b910f2e7d4b178e6e64a64f&pid=1-s2.0-S0167488919301661-main.pdf
Languageen angielski
Score (nominal)140
Score sourcejournalList
Publication indicators WoS Citations = 1; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.168; WoS Impact Factor: 2018 = 4.739 (2) - 2018=5.281 (5)
Citation count*
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FinansowanieThis work was supported by the Polish National Science Centre(NCN), grant number UMO-2012/07/D/NZ1/00523
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