Search

Cells experience mechanical stresses in different physiological and pathological settings. Clathrin-coated structures (CCSs) are sensitive to such perturbations in a way that often results in a mechanical impairment of endocytic budding. Compressive stress is a mechanical perturbation that leads to increased membrane tension and promotes proliferative signals. Here, we report that compression leads to CCSs frustration and that CCSs are required to potentiate receptor-mediated signaling in these conditions. We show that cell compression stalled CCSs dynamics and slowed down the dynamic exchange of CCSs building blocks. As previously reported, compression-induced paracrine activation of the epidermal growth factor receptor (EGFR) was the primary cause of ERK activation in these conditions. We observed that the EGFR was efficiently recruited at CCSs upon compression and that CCSs were required for full ERK activation. In addition, we demonstrated that compression-induced frustrated CCSs could also increase ligand-dependent signaling of other receptors. We thus propose that CCS frustration resulting from mechanical perturbations can potentiate signaling through different receptors with potential important consequences on cell adaptation to its environment.

Cells experience mechanical stresses in different physiological and pathological settings. Clathrin-coated structures (CCSs) are sensitive to such perturbations in a way that often results in a mechanical impairment of their capacity to bud, ultimately impairing endocytosis. Compressive stress is a particular mechanical perturbation that leads to increased membrane tension and promotes proliferative signals. Here, we report that compression leads to CCSs frustration and that CCSs are required to potentiate receptor-mediated signaling in these conditions. We first confirmed that pressure stalls CCSs dynamics and showed that it also slows down the dynamic exchange of CCSs building blocks. As previously reported, compression-induced paracrine activation of the epidermal growth factor receptor (EGFR) was the primary cause of ERK activation in these conditions. We observed that the EGFR was efficiently recruited at CCSs upon compression and that CCSs were required for full ERK activation. In addition, we demonstrated that compression-induced frustrated CCSs could also serve as signaling platforms for the hepatocyte growth factor receptor (HGFR), provided HGF was present in the medium. We thus propose that, besides the particular case of EGFR paracrine activation, CCS frustration resulting from mechanical perturbations can potentiate signaling through different receptors with potential important consequences on cell adaptation to its environment.

Cells experience mechanical stresses in different physiological and pathological settings. Clathrin-coated structures (CCSs) are sensitive to such perturbations in a way that often results in a mechanical impairment of endocytic budding. Compressive stress is a mechanical perturbation that leads to increased membrane tension and promotes proliferative signals. Here, we report that compression leads to frustration of CCSs and that CCSs are required to potentiate receptor-mediated signaling in these conditions. We show that cell compression stalled CCS dynamics and slowed down the dynamic exchange of CCS components. As previously reported, compression-induced paracrine activation of the epidermal growth factor receptor (EGFR) was the primary cause of ERK (ERK1 and ERK2, also known as MAPK3 and MAPK1, respectively) activation in these conditions. We observed that EGFR was efficiently recruited at CCSs upon compression and that CCSs were required for full ERK activation. In addition, we demonstrated that compression-induced frustrated CCSs could also increase ligand-dependent signaling of other receptors. We thus propose that CCS frustration resulting from mechanical perturbations can potentiate signaling through different receptors, with potential important consequences for the adaptation of the cell to its environment.This article has an associated First Person interview with the first author of the paper.