Vulval development is induced by the gonadal anchor cell (AC), which secretes the LIN-3 EGF ligand. Among the six epidermal vulval precursor cells (VPCs), P6.p lies closest to the AC and thus receives the highest amount of the inductive LIN-3 signal. LET-23 EGFR in the basolateral compartment of P6.p binds to LIN-3 and activates the conserved RAS/MAPK signaling pathway, resulting in the induction of the primary vulval cell fate. Correct localization of LET-23 is therefore a prerequisite for proper vulval fate specification. ERM-1, a member of the Ezrin/Radixin/Moesin (ERM) protein family, was identified in a screen for regulators of LET-23 EGFR localization. Members of the ERM protein family link plasma membrane proteins to the F-actin cytoskeleton and thus regulate the membrane distribution and activity of various receptors. Our genetic analysis indicates that ERM-1 acts as a negative regulator of the EGFR/RAS/MAPK pathway. Furthermore, by analysis of a functional LET-23::GFP translational fusion we find that in wild type worms, LET-23::GFP is localized in the basolateral and apical membrane compartment of P6.p, while in
erm-1(
tm677) mutants, LET-23::GFP accumulates in intracellular punctate as well. Moreover, we observe a physical interaction between ERM-1 and LET-23 in co-immunoprecipitation and pull-down experiments using a recombinant N-terminal fragment of ERM-1, and a functional ERM-1::CFP reporter which localizes predominantly to the basolateral membrane compartment of the VPCs. Taken together, we propose that ERM-1 keeps LET-23 in a distinct basolateral membrane compartment of the VPCs where LET-23 cannot be activated by LIN-3. In
erm-1 mutants, a larger fraction of LET-23 is exposed to the inductive LIN-3 signal, resulting in an increased rate of receptor endocytosis. Our findings reveal a novel function of ERM family proteins controlling cell fate specification.