Control of cell death/survival balance by the MET dependence receptor

Leslie Duplaquet (1) , Catherine Leroy (1) , Audrey Vinchent (1) , Sonia Paget (1) , Jonathan Lefebvre (1) , Fabien Vanden Abeele (2) , Steve S. Lancel (3) , Florence Giffard (4) , Réjane Paumelle (3) , Gabriel Bidaux (5) , Laurent Heliot (5) , Laurent Poulain (4) , Alessandro Furlan (1, 5) , David Tulasne (1)

1 M3T - Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161
2 PHYCELL - Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003
3 RNMCD - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011
4 ANTICIPE - Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers
5 PhLAM - Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523

Control of cell death/survival balance is an important feature to maintain tissue homeostasis. Dependence receptors are able to induce either survival or cell death in presence or absence of their ligand, respectively. However, their precise mechanism of action and their physiological importance are still elusive for most of them including the MET receptor. We evidence that pro-apoptotic fragment generated by caspase cleavage of MET localizes to the mitochondria-associated membrane region. This fragment triggers a calcium transfer from endoplasmic reticulum to mitochondria, which is instrumental for the apoptotic action of the receptor. Knock-in mice bearing a mutation of MET caspase cleavage site highlighted that p40MET production is important for FAS-driven hepatocyte apoptosis, and demonstrate that MET acts as a dependence receptor in vivo. Our data shed light on new signaling mechanisms for dependence receptors' control of cell survival/death balance, which may offer new clues for the pathophysiology of epithelial structures.

Domaines: Sciences du Vivant [q-bio]

Leslie Duplaquet, Catherine Leroy, Audrey Vinchent, Sonia Paget, Jonathan Lefebvre, et al.. Control of cell death/survival balance by the MET dependence receptor. eLife, 2020, 9, pp.e50041. ⟨10.7554/eLife.50041⟩. ⟨hal-03060380⟩