“Glyco-sulfo barcodes” regulate chemokine receptor function
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
“Glyco-sulfo barcodes” regulate chemokine receptor function. / Verhallen, Lisa; Lackman, Jarkko J.; Wendt, Rikke; Gustavsson, Martin; Yang, Zhang; Narimatsu, Yoshiki; Sørensen, Daniel M.; Lafferty, Kato Mac; Gouwy, Mieke; Marques, Pedro E.; Hjortø, Gertrud M.; Rosenkilde, Mette M.; Proost, Paul; Goth, Christoffer K.
In: Cellular and Molecular Life Sciences, Vol. 80, No. 2, 55, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - “Glyco-sulfo barcodes” regulate chemokine receptor function
AU - Verhallen, Lisa
AU - Lackman, Jarkko J.
AU - Wendt, Rikke
AU - Gustavsson, Martin
AU - Yang, Zhang
AU - Narimatsu, Yoshiki
AU - Sørensen, Daniel M.
AU - Lafferty, Kato Mac
AU - Gouwy, Mieke
AU - Marques, Pedro E.
AU - Hjortø, Gertrud M.
AU - Rosenkilde, Mette M.
AU - Proost, Paul
AU - Goth, Christoffer K.
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Chemokine receptor
KW - G protein-coupled receptor
KW - O-glycosylation
KW - Tyrosine sulfation
UR - http://www.scopus.com/inward/record.url?scp=85147269322&partnerID=8YFLogxK
U2 - 10.1007/s00018-023-04697-9
DO - 10.1007/s00018-023-04697-9
M3 - Journal article
C2 - 36729338
AN - SCOPUS:85147269322
VL - 80
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 2
M1 - 55
ER -
ID: 335679373