Biology subjects

Mege, R.-M.

Publications and source records attributed to Mege, R.-M..

21 records · Page 2Linked to original sources

bioRxiv2018

Enhanced cell-cell contact stability upon Fibroblast Growth factor Receptor/N-cadherin cross-talk

N-cadherin adhesion has been reported to enhance cancer and neuronal cell migration either by mediating actomyosin-based force transduction or initiating Fibroblast Growth Factor Receptor (FGFR)-dependent biochemical signalling. Here we show that FGFR1 reduces N-cadherin-mediated cell migration. Both proteins are co-stabilised at cell-cell contacts through direct interaction. As a consequence, cell adhesion is strengthened, limiting the migration of cells on N-cadherin. Both the inhibition of migration and the stabilisation of cell adhesions require the FGFR activity stimulated by N-cadherin engagement. FGFR1 stabilises N-cadherin at the cell membrane through a pathway involving Src and p120. Moreover, FGFR1 stimulates the anchoring of N-cadherin to actin. We found that the migratory behaviour of cells depends on an optimum balance between FGFR-regulated N-cadherin adhesion and actin dynamics. Based on these findings we propose a positive feedback loop between N-cadherin and FGFR at adhesion sites limiting N-cadherin-based single cell migration.

cell biology↗

bioRxiv2018

Local Contractions Test Rigidity of E-Cadherin Adhesions

E-cadherin is a major cell-cell adhesion molecule involved in mechanotransduction at cell-cell contacts in tissues. Since epithelial cells respond to rigidity and tension in the tissue through E-cadherin, there must be active processes that test and respond to the mechanical properties of these adhesive contacts. Using sub-micrometer, E-cadherin-coated PDMS pillars, we find that cells generate local contractions between E-cadherin adhesions and pull to a constant distance for a constant duration, irrespective of pillar rigidity. These cadherin contractions require non-muscle myosin IIB, tropomyosin 2.1, -catenin and binding of vinculin to -catenin; plus, they are correlated with rigidity-dependent cell spreading. Without contractions, cells fail to spread to different areas on soft and rigid surfaces and to maintain monolayer integrity. We further observe that cadherin contractions enable cells to test myosin IIA-mediated tension of neighboring cells, and sort out myosin IIA-depleted cells. Thus, we suggest that epithelial cells test and respond to the mechanical characteristics of neighboring cells through cadherin contractions.

cell biology↗

bioRxiv2017

Force-Dependent Binding Of Vinculin To α-Catenin Regulates Cell-Cell Contacts Stability And Collective Cell Behavior

The shaping of a multicellular body and repair of adult tissues require fine-tuning of cell adhesion, cell mechanics and intercellular transmission of mechanical load. Adherens junctions (AJs) are the major intercellular junctions by which cells sense and exert mechanical force on each other. However, how AJs adapt to mechanical stress and how this adaptation contributes to cell-cell cohesion and eventually to tissue-scale dynamics and mechanics remains largely unknown. Here, by analyzing the tension-dependent recruitment of vinculin, -catenin and F-actin as a function of stiffness, as well as the dynamics of GFP-tagged wild-type and mutated -catenins, altered for their binding capability to vinculin, we demonstrate that the force-dependent binding of vinculin stabilizes -catenin and is responsible for AJ adaptation to force. Challenging cadherin complexes mechanical coupling with magnetic tweezers, and cell-cell cohesion during collective cell movements, further highlight that tension-dependent adaptation of AJs regulates cell-cell contact dynamics and coordinated collective cell migration. Altogether, these data demonstrate that the force-dependent -catenin/vinculin interaction, manipulated here by mutagenesis and mechanical control, is a core regulator of AJ mechanics and long-range cell-cell interactions.\n\nSummary statementCombining cell biology and biomechanical analysis, we show here that the coupling between cadherin complexes and actin trough tension-dependent -catenin/vinculin association is regulating AJ stability and dynamics as well as tissue-scale mechanics.

cell biology↗