“Glyco-sulfo barcodes” regulate chemokine receptor function
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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.
|Cellular and Molecular Life Sciences
|Udgivet - 2023
This work was supported by Lundbeck Foundation (R322-2019-2171) and Novo Nordisk Foundation (NNF20OC0064565) to CG and MMR. This project received support from a C1 grant from KU Leuven (C16/17/010) and two research grants from FWO-Vlaanderen (G080818N and G036423N).
This work was supported by Lundbeck Foundation (R322-2019-2171) to CG. PEM holds a Marie Skłodowska-Curie Actions (MSCA) postdoctoral fellowship of the European Union (EU) (ref ESA-D6247-MSCA-IF-2018 “Impact”) and this project received support from a C1 grant from the Katholic University of Leuven (KU Leuven) (C16/17/010) and two research grants from Fonds Wetenschappelijk onderzoek (FWO) Vlaanderen (G080818N and G036423N).
© 2023, The Author(s).
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