The dimeric form of CXCL12 binds to atypical chemokine receptor 1.


Journal

Science signaling
ISSN: 1937-9145
Titre abrégé: Sci Signal
Pays: United States
ID NLM: 101465400

Informations de publication

Date de publication:
17 08 2021
Historique:
entrez: 18 8 2021
pubmed: 19 8 2021
medline: 15 1 2022
Statut: epublish

Résumé

The pleiotropic chemokine CXCL12 is involved in diverse physiological and pathophysiological processes, including embryogenesis, hematopoiesis, leukocyte migration, and tumor metastasis. It is known to engage the classical receptor CXCR4 and the atypical receptor ACKR3. Differential receptor engagement can transduce distinct cellular signals and effects as well as alter the amount of free, extracellular chemokine. CXCR4 binds both monomeric and the more commonly found dimeric forms of CXCL12, whereas ACKR3 binds monomeric forms. Here, we found that CXCL12 also bound to the atypical receptor ACKR1 (previously known as Duffy antigen/receptor for chemokines or DARC). In vitro nuclear magnetic resonance spectroscopy and isothermal titration calorimetry revealed that dimeric CXCL12 bound to the extracellular N terminus of ACKR1 with low nanomolar affinity, whereas the binding affinity of monomeric CXCL12 was orders of magnitude lower. In transfected MDCK cells and primary human Duffy-positive erythrocytes, a dimeric, but not a monomeric, construct of CXCL12 efficiently bound to and internalized with ACKR1. This interaction between CXCL12 and ACKR1 provides another layer of regulation of the multiple biological functions of CXCL12. The findings also raise the possibility that ACKR1 can bind other dimeric chemokines, thus potentially further expanding the role of ACKR1 in chemokine retention and presentation.

Identifiants

pubmed: 34404752
pii: 14/696/eabc9012
doi: 10.1126/scisignal.abc9012
pmc: PMC9015690
mid: NIHMS1796055
pii:
doi:

Substances chimiques

ACKR1 protein, human 0
CXCL12 protein, human 0
Chemokine CXCL12 0
Duffy Blood-Group System 0
Receptors, CXCR4 0
Receptors, Cell Surface 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAID NIH HHS
ID : R37 AI058072
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI058072
Pays : United States
Organisme : Wellcome Trust
ID : 200817/Z/16/Z
Pays : United Kingdom
Organisme : NIH HHS
ID : S10 OD020000
Pays : United States
Organisme : Versus Arthritis
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : T32 GM080202
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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Auteurs

Julia C Gutjahr (JC)

Centre for Microvascular Research, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.

Kyler S Crawford (KS)

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Davin R Jensen (DR)

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Prachi Naik (P)

Centre for Microvascular Research, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.

Francis C Peterson (FC)

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Guerric P B Samson (GPB)

Biotechnology Institute Thurgau (BITg), University of Konstanz, 8280 Kreuzlingen, Switzerland.

Daniel F Legler (DF)

Biotechnology Institute Thurgau (BITg), University of Konstanz, 8280 Kreuzlingen, Switzerland.
Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland.

Johan Duchene (J)

Institute for Cardiovascular Prevention, Ludwig-Maximilians University, 80336 Munich, Germany.

Christopher T Veldkamp (CT)

Department of Chemistry, University of Wisconsin-Whitewater, Whitewater, WI 53190, USA.

Antal Rot (A)

Centre for Microvascular Research, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. bvolkman@mcw.edu a.rot@qmul.ac.uk.
Institute for Cardiovascular Prevention, Ludwig-Maximilians University, 80336 Munich, Germany.
Centre for Inflammation and Therapeutic Innovation, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.

Brian F Volkman (BF)

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA. bvolkman@mcw.edu a.rot@qmul.ac.uk.

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