Optogenetic control of a GEF of RhoA uncovers a signaling switch from retraction to protrusion.

ABSTRACT: The ability of a single protein to trigger different functions is an assumed key feature of cell signaling, yet there are very few examples demonstrating it. Here, using an optogenetic tool to control membrane localization of RhoA nucleotide exchange factors (GEFs), we present a case where the same protein can trigger both protrusion and retraction when recruited to the plasma membrane, polarizing the cell in two opposite directions. We show that the basal concentration of the GEF prior to activation predicts the resulting phenotype. A low concentration leads to retraction, whereas a high concentration triggers protrusion. This unexpected protruding behavior arises from the simultaneous activation of Cdc42 by the GEF and sequestration of active RhoA by the GEF PH domain at high concentrati

SUBMITTER: de Seze J 

PROVIDER: S-EPMC12113259 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature