Solo regulates the localization and activity of LARG for actin cytoskeletal remodeling in cell-substrate adhesions.

In response to external mechanical stimuli, cells remodel their actin cytoskeleton. Solo, a Rho guanine nucleotide exchange factor (RhoGEF), is involved in mechanical stress responses via cell-substrate adhesions. Using BioID, we identified PDZ-RhoGEF (PRG), a member of the RGS-RhoGEF (regulator of G protein signaling domain-containing RhoGEFs) family, as a Solo-interacting protein. Moreover, we found that Solo regulates PRG during the mechanical stress response. Furthermore, we identified leukemia-associated RhoGEF (LARG), another RGS-RhoGEF member, as a Solo-interacting protein; however, the functional role of this interaction remains unknown. Therefore, in this study, we investigated the interaction between Solo and LARG and found that LARG localizes to Solo accumulation sites at the basal plane and that LARG is required for Solo-induced actin polymerization. Additionally, Solo is required to maintain LARG activity in cells, and this interaction is related to actin regulation in response to substrate stiffness. We further investigated the relationship between LARG and PRG as a function of Solo. We noted that the double knockdown of PRG and LARG suppressed Solo-induced actin polymerization to the same extent or more than every single knockdown, indicating that these signaling pathways cooperatively regulate Solo-induced actin polymerization.