“Glyco-sulfo barcodes” regulate chemokine receptor function

Lisa Verhallen, Jarkko J. Lackman, Rikke Wendt, Martin Gustavsson, Zhang Yang, Yoshiki Narimatsu, Daniel M. Sørensen, Kato Mac Lafferty, Mieke Gouwy, Pedro E. Marques, Gertrud M. Hjortø, Mette M. Rosenkilde, Paul Proost, Christoffer K. Goth*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

6 Citations (Scopus)
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Abstract

Chemokine ligands and receptors regulate the directional migration of leukocytes. Post-translational modifications of chemokine receptors including O-glycosylation and tyrosine sulfation have been reported to regulate ligand binding and resulting signaling. Through in silico analyses, we determined potential conserved O-glycosylation and sulfation sites on human and murine CC chemokine receptors. Glyco-engineered CHO cell lines were used to measure the impact of O-glycosylation on CC chemokine receptor CCR5, while mutation of tyrosine residues and treatment with sodium chlorate were performed to determine the effect of tyrosine sulfation. Changing the glycosylation or tyrosine sulfation on CCR5 reduced the receptor signaling by the more positively charged CCL5 and CCL8 more profoundly compared to the less charged CCL3. The loss of negatively charged sialic acids resulted only in a minor effect on CCL3-induced signal transduction. The enzymes GalNAc-T1 and GalNAc-T11 were shown to be involved in the process of chemokine receptor O-glycosylation. These results indicate that O-glycosylation and tyrosine sulfation are involved in the fine-tuning and recognition of chemokine interactions with CCR5 and the resulting signaling.

Original languageEnglish
Article number55
JournalCellular and Molecular Life Sciences
Volume80
Issue number2
Number of pages18
ISSN1420-682X
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Chemokine receptor
  • G protein-coupled receptor
  • O-glycosylation
  • Tyrosine sulfation

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