“Glyco-sulfo barcodes” regulate chemokine receptor function

• DOI: 10.1007/s00018-023-04697-9
• Publication Date: 2023-02-02T05:07:54Z
• Authors: 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
• Keywords: CCR1; CCL25; CCL21

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