Fibroblast growth factor receptors (FGFRs) are cell-surface receptor tyrosine-kinases (RTKs) that phosphorylate specific tyrosine residues to trigger downstream responses. In C. elegans, the sole FGFR, EGL-15, is involved in multiple functions, including serving as a receptor for a chemoattractive guidance cue for the migrating sex myoblasts, ensuring that the egg-laying muscles are in functional positions. EGL-15 also regulates internal fluid levels: hyperactivation of EGL-15 causes excessive accumulation of clear fluid inside the worm's body (the Clr phenotype). The isolation of Suppressor Of Clr (soc) mutants has led to the identification of many of the core components of EGL-15 signaling: the original set of soc mutations identified the Grb2/SEM-5 adaptor protein that links RTK signaling to the RAS/MAPK pathway.
egl-15(
n1457) is a nonsense mutation that is predicted to truncate EGL-15's carboxy-terminal domain (?CTD) and eliminates the two known direct SEM-5 binding sites on EGL-15. Interestingly,
n1457 confers an Egl phenotype, but does not confer a Soc phenotype. Mutation of the two YXNX SEM-5 binding sites in the CTD mimics the phenotype of
n1457. Since SEM-5 is required for EGL-15 signaling, these data suggest the existence of an alternate pathway that links EGL-15 to SEM-5/Grb2 in its role in mediating fluid homeostasis. To identify components of this alternate pathway, we repeated the screen for Soc mutants in an
n1457(?CTD) background. Preliminary characterization of these enhancer alleles indicates that the screen was successful in two ways. First, the behavior of the enhancer alleles supports two cooperative pathways that transduce EGL-15 signaling: many of the enhancer mutations show only partial Soc phenotypes on their own, and are enhanced by the
n1457(?CTD) mutation. Second, the characterization of these soc enhancer mutations suggests that they define up to three new soc genes that potentially function in the alternate pathway. Further genetic analysis and whole-genome sequencing will be used to identify the molecular identities of these new FGFR signaling genes.