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Proteoglycan profiling of human, rat and mouse insulin-secreting cells.

Authors
  • Nikpour, Mahnaz1
  • Nilsson, Jonas1, 2, 3
  • Persson, Andrea1
  • Noborn, Fredrik1
  • Vorontsov, Egor2
  • Larson, Göran1, 2, 3
  • 1 Department of Laboratory Medicine, Sahlgrenska Academy, University of Gothenburg, Bruna Stråket 16, SE 413 45 Gothenburg, Sweden. , (Sweden)
  • 2 Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 9E, SE 405 30 Gothenburg, Sweden. , (Sweden)
  • 3 Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Bruna Stråket 16, SE 413 45 Gothenburg, Sweden. , (Sweden)
Type
Published Article
Journal
Glycobiology
Publisher
Oxford University Press
Publication Date
Sep 09, 2021
Volume
31
Issue
8
Pages
916–930
Identifiers
DOI: 10.1093/glycob/cwab035
PMID: 33997891
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Proteoglycans (PGs) are proteins with glycosaminoglycan (GAG) chains, such as chondroitin sulfate (CS) or heparan sulfate (HS), attached to serine residues. We have earlier shown that prohormones can carry CS, constituting a novel class of PGs. The mapping of GAG modifications of proteins in endocrine cells may thus assist us in delineating possible roles of PGs in endocrine cellular physiology. With this aim, we applied a glycoproteomic approach to identify PGs, their GAG chains and their attachment sites in insulin-secreting cells. Glycopeptides carrying GAG chains were enriched from human pancreatic islets, rat (INS-1 832/13) and mouse (MIN6, NIT-1) insulinoma cell lines by exchange chromatography, depolymerized with GAG lyases, and analyzed by nanoflow liquid chromatography tandem mass spectrometry. We identified CS modifications of chromogranin-A (CgA), islet amyloid polypeptide, secretogranin-1 and secretogranin-2, immunoglobulin superfamily member 10, and protein AMBP. Additionally, we identified two HS-modified prohormones (CgA and secretogranin-1), which was surprising, as prohormones are not typically regarded as HSPGs. For CgA, the glycosylation site carried either CS or HS, making it a so-called hybrid site. Additional HS sites were found on syndecan-1, syndecan-4, nerurexin-2, protein NDNF and testican-1. These results demonstrate that several prohormones, and other constituents of the insulin-secreting cells are PGs. Cell-targeted mapping of the GAG glycoproteome forms an important basis for better understanding of endocrine cellular physiology, and the novel CS and HS sites presented here provide important knowledge for future studies. © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

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