G Protein-Coupled Estrogen Receptor Regulates Actin Cytoskeleton Dynamics to Impair Cell Polarization
Dariusz Lachowski, Ernesto Cortés, Carlos Matellan, Alistair Rice, David A. Lee, Stephen D. Thorpe, Armando E. del Río Hernández
Abstract
Mechanical forces regulate cell functions through multiple pathways. G protein-coupled estrogen receptor (GPER) is a seven transmembrane receptor that is ubiquitously expressed across tissues and mediates the acute cellular response to estrogens. Here, we demonstrate an unidentified role of GPER as a cellular mechanoregulator. GPER signaling controls the assembly of stress fibers, the dynamics of the associated focal adhesions, and cell polarization via RhoA. GPER activation inhibits F-actin polymerization, and subsequently triggers a negative feedback that transcriptionally suppresses the expression of monomeric G-actin. Given the broad expression of GPER and the range of cytoskeletal changes modulated by this receptor, our findings position GPER as a key player in mechanotransduction.