Katelyn Flitcroft, “Cell Specific Mechanisms of Fibroblast Growth Factor Signaling in C. elegans”
Mentor: Claire de la Cova, Biological Sciences
Poster #60

Fibroblast Growth Factor Receptors (FGFRs) belong to the Receptor Tyrosine Kinase family and are necessary for animal development and a wide range of cellular functions. Ligand binding to FGFRs induces dimerization and activation of the intracellular tyrosine kinase domain. This leads to activation of multiple signaling proteins and pathways, including the GTPase RAS and the kinases RAF, MEK, and ERK. The Caenorhabditis elegans FGFR, EGL-15, is expressed in the sex myoblast and the hypodermis, where it is needed for sex myoblast migration and fluid homeostasis, respectively. Previous studies demonstrated that SEM-5, an adaptor protein required for RAS activation, interacts directly with the EGL-15 C-terminal domain (CTD). This interaction is required in the sex myoblast, as an EGL-15 mutant with a truncated CTD, which we term egl-15ΔCTD, does not permit cell migration. In the hypodermis, the EGL-15 CTD is not required, as the same mutant can still maintain fluid homeostasis. To quantify these results, we used ERK activity as a metric to assess the impact of the egl-15ΔCTD mutant. We hypothesized that ERK activation by the EGL-15ΔCTD mutant would be reduced in the sex myoblast yet unchanged in the hypodermis. To measure ERK activity, we used an in vivo, fluorescent biosensor termed the ERK Kinase Translocation Reporter (ERK-KTR). The ERK-KTR is a substrate of ERK and its phosphorylation state is monitored through nuclear/cytoplasmic localization within the cell. In the egl-15ΔCTD mutant, we observed that ERK activity was significantly reduced in the sex myoblast. However, ERK activity was moderate but significantly increased in the hypodermis. Our results suggest that EGL-15 uses cell specific signaling mechanisms, relying on its CTD for signaling in the sex myoblast, and a CTD-independent mechanism for signaling in the hypodermis.