UNC-103 is the C. elegans orthologue of the ether-a-go-go related gene, a voltage-gated potassium channel which contributes to cellular excitability. UNC-103 is required for normal egg-laying and brood size. Loss-of-function (lf) mutations in UNC-103 result in a constitutive egg-laying phenotype and decreased brood size, while a putative gain-of-function allele,
unc-103(
n500), is defective in egg-laying. The
unc-103(
n500) strain was used as the background for an RNAi screen of Chromosome I designed to identify genes that modify UNC-103 activity. In this screen we identified EAT-16 as a modulator of UNC-103 activity. Other researchers have shown that EAT-16 is an upstream regulator of EGL-30, a Gq alpha subunit. We constructed a double mutant with a reduction-of-function mutation in
eat-16, and
unc-103(
n500) and observed partial rescue of the egg-laying defects associated with
unc-103(
n500). We hypothesized that EAT-16 modulation of UNC-103 activity occurs through EAT-16 modulation of the EGL-30 signaling pathway. In support of this hypothesis we find that a reduction-of-function mutation in
egl-30 phenocopies the egg-laying defects of
unc-103(
n500) and a gain-of-function mutation in
egl-30 phenocopies the constitutive egg-laying phenotype of
unc-103(lf) mutations. Furthermore, a double mutant with
unc-103(lf) and a reduction-of-function mutation in
egl-30 partially rescues the egg-laying defects associated with reduced EGL-30 activity. UNC-103 may be a direct target of Gq signaling molecules or an indirect modifier. We favor the former hypothesis as in vitro biochemical assays demonstrate that UNC-103 is able to physically interact with PIP2, a downstream component of EAT-16/EGL-30 signaling. Our current model views UNC-103 as a downstream effector for EAT-16/EGL-30 signaling that influences egg-laying through effects on cell excitability. We are currently analyzing mutations in other components of the Gq pathway for functional interaction with UNC-103.