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>