Cooperative regulation of adherens junction expansion through epidermal growth factor receptor activation

Abstract

The mechanisms controlling the dynamics of expansion of adherens junctions are significantly less understood than those controlling their static properties. Here, we report that for suspended cell aggregates, the time to form a new junction between two cells speeds up with the number of junctions that the cells are already engaged in. Upon junction formation, the activation of the Epidermal Growth Factor Receptor (EGFR) distally affects the actin turnover dynamics of the cell-free cortex. The “primed” actin cortex results in a faster expansion of the subsequent new junctions. In such aggregates, we show that this mechanism results in a cooperative acceleration of the junction expansion dynamics (kinetype) but leaves the cell contractility, and hence the final junction size (phenotype), unaltered.

Cortical ductility governs cell-cell adhesion mechanics

“…[14][15][16] . For example, cadherin recruitment leads to biochemical and biophysical modulation of cortical properties via various Rho GTPases [16][17][18] . In turn, cortical tension drives the mechanosensitive recruitment of cadherins at adherens junction 15 .…”

E-cadherin-dependent phosphorylation of EGFR governs a homeostatic feedback loop controlling intercellular junction viscosity and collective migration modes

“…We previously reported that E-cad-dependent phosphorylation of EGFR in suspended cell doublets increases the velocity of de-novo junction formation 8 and the toughness of their adhesion 16 . In all cases, the microscopic dynamics of the actin cortex are associated with a change in cell deformability, with minimal impact on cortical tension.…”

“…While viscous dissipation in the actin network is commonly regarded as a constant passive parameter in cell migration in both 2D and 3D contexts, there is limited knowledge concerning the regulation of dissipative forces arising from viscous drag between cells during collective rearrangement. Here, we found that the phosphorylation of Epithelial Growth Factor Receptor (EGFR) downstream of de novo E-cadherin adhesion 7, 8 orchestrates a feedback loop, thereby governing intercellular viscosity via the Rac pathway regulating actin dynamics. Our findings highlight how the E-cadherin-dependent EGFR activity controls the migration mode of collective cell movements independently of intercellular tension.…”

“…We subsequently delved into the molecular mechanisms underlying this phenomenon. The absence of the soluble ligand EGF and the specific phosphorylation of Y845 suggested an E-cadherin (Ecad)-dependent activation of EGFR 7,8,11 . Confluent patches of WT-MDCK cells displayed a two-fold decrease in apical pEGFR compared to sub-confluent patches (27.6 ± 11.1 A.U.…”