1. The atypical chemokine receptor 3 interacts with Connexin 43 inhibiting astrocytic gap junctional intercellular communication
- Author
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Fumagalli, Amos, Heuninck, Joyce, Pizzoccaro, Anne, Moutin, Enora, Koenen, Joyce, Séveno, Martial, Durroux, Thierry, Junier, Marie Pierre, Schlecht-Louf, Géraldine, Bachelerie, Francoise, Schütz, Dagmar, Stumm, Ralf, Smit, Martine J., Guérineau, Nathalie C., Chaumont-Dubel, Séverine, Marin, Philippe, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Amsterdam [Amsterdam] (UvA), Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Division of Medicinal Chemistry, Vrije Universiteit Amsterdam [Amsterdam] (VU), BioCampus (BCM), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Jena University Hospital [Jena], CNRS, INSERM, Université de Montpellier, Fondation pour la Recherche Médicale, European Project: 641833,H2020,H2020-MSCA-ITN-2014,ONCORNET(2015), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Guerineau, Nathalie C., ONCOgenic Receptor Network of Excellence and Training - ONCORNET - - H20202015-01-01 - 2018-12-31 - 641833 - VALID, AIMMS, and Medicinal chemistry
- Subjects
Cell biology ,Science ,[SDV]Life Sciences [q-bio] ,Cell Communication ,Connexins ,Article ,Mice ,SDG 3 - Good Health and Well-being ,Animals ,Humans ,Protein Interaction Domains and Motifs ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Gene Knock-In Techniques ,lcsh:Science ,Cell Proliferation ,Mice, Knockout ,Receptors, CXCR ,Gap Junctions ,Glial biology ,[SDV] Life Sciences [q-bio] ,Mice, Inbred C57BL ,HEK293 Cells ,Astrocytes ,Connexin 43 ,lcsh:Q ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Glioblastoma ,Signal Transduction - Abstract
The atypical chemokine receptor 3 (ACKR3) plays a pivotal role in directing the migration of various cellular populations and its over-expression in tumors promotes cell proliferation and invasiveness. The intracellular signaling pathways transducing ACKR3-dependent effects remain poorly characterized, an issue we addressed by identifying the interactome of ACKR3. Here, we report that recombinant ACKR3 expressed in HEK293T cells recruits the gap junction protein Connexin 43 (Cx43). Cx43 and ACKR3 are co-expressed in mouse brain astrocytes and human glioblastoma cells and form a complex in embryonic mouse brain. Functional in vitro studies show enhanced ACKR3 interaction with Cx43 upon ACKR3 agonist stimulation. Furthermore, ACKR3 activation promotes β-arrestin2- and dynamin-dependent Cx43 internalization to inhibit gap junctional intercellular communication in primary astrocytes. These results demonstrate a functional link between ACKR3 and gap junctions that might be of pathophysiological relevance., The atypical chemokine receptor 3 (ACKR3) is known to regulate cell migration, but the underlying mechanisms are unclear. Here, the authors show, from an interactome analysis, ACKR3 association with the gap junction protein Connexin 43 in vivo and ACKR3-mediated inhibition of astrocyte gap junctional communication.
- Published
- 2020