The atypical chemokine receptor 3 interacts with Connexin 43 inhibiting astrocytic gap junctional intercellular communication

Amos Fumagalli, Joyce Heuninck, Anne Pizzoccaro, Enora Moutin, Joyce Koenen, Martial Séveno, Thierry Durroux, Marie Pierre Junier, Géraldine Schlecht-Louf, Francoise Bachelerie, Dagmar Schütz, Ralf Stumm, Martine J. Smit, Nathalie C. Guérineau, Séverine Chaumont-Dubel, Philippe Marin*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Article number4855
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Volume11
Issue number1
Early online date25 Sep 2020
DOIs
Publication statusPublished - 1 Dec 2020

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