10.6084/m9.figshare.3997221.v1 Pierre-Michaël Coly Pierre-Michaël Coly Nicolas Perzo Nicolas Perzo Vadim Le Joncour Vadim Le Joncour Céline Lecointre Céline Lecointre Marie-Thérèse Schouft Marie-Thérèse Schouft Laurence Desrues Laurence Desrues Marie-Christine Tonon Marie-Christine Tonon Olivier Wurtz Olivier Wurtz Pierrick Gandolfo Pierrick Gandolfo Hélène Castel Hélène Castel Fabrice Morin Fabrice Morin Chemotactic G protein-coupled receptors control cell migration by repressing autophagosome biogenesis Taylor & Francis Group 2016 autophagosome biogenesis cell adhesion chemotactic migration CXCR4 GPCR urotensin II 2016-10-07 14:34:21 Dataset https://tandf.figshare.com/articles/dataset/Chemotactic_G_protein-coupled_receptors_control_cell_migration_by_repressing_autophagosome_biogenesis/3997221 <p>Chemotactic migration is a fundamental behavior of cells and its regulation is particularly relevant in physiological processes such as organogenesis and angiogenesis, as well as in pathological processes such as tumor metastasis. The majority of chemotactic stimuli activate cell surface receptors that belong to the G protein-coupled receptor (GPCR) superfamily. Although the autophagy machinery has been shown to play a role in cell migration, its mode of regulation by chemotactic GPCRs remains largely unexplored. We found that ligand-induced activation of 2 chemotactic GPCRs, the chemokine receptor CXCR4 and the urotensin 2 receptor UTS2R, triggers a marked reduction in the biogenesis of autophagosomes, in both HEK-293 and U87 glioblastoma cells. Chemotactic GPCRs exert their anti-autophagic effects through the activation of CAPNs, which prevent the formation of pre-autophagosomal vesicles from the plasma membrane. We further demonstrated that CXCR4- or UTS2R-induced inhibition of autophagy favors the formation of adhesion complexes to the extracellular matrix and is required for chemotactic migration. Altogether, our data reveal a new link between GPCR signaling and the autophagy machinery, and may help to envisage therapeutic strategies in pathological processes such as cancer cell invasion.</p>