Regulators of G protein signaling (RGS proteins) act as G protein GTPase activators in vitro, but little is known about why these G protein inhibitors exist. C. elegans egg laying is controlled by antagonistic signaling of the G proteins GOA-1 (Go) and EGL-30 (Gq), which are negatively regulated by the RGS proteins EGL-10 and EAT-16 respectively1, 2. In a survey of the functions of all 13 C. elegans RGS genes, we found that overexpression of
egl-10,
rgs-1, or
rgs-2 mimics the loss-of-function phenotype of
goa-1. Thus, these three RGS proteins might all regulate the G protein GOA-1. We generated deletion alleles for both
rgs-1 and
rgs-2; neither single nor double mutants of
rgs-1 and
rgs-2 strongly affect egg laying under constant food conditions. However,
rgs-1;
rgs-2 double mutants fail to rapidly induce egg laying when re-fed after egg laying has been halted by starvation. This defect is not seen in either
egl-10 or
eat-16 RGS mutants. Although
egl-10 and
eat-16 mutants exhibit abnormal egg-laying behavior, they still rapidly adjust this behavior according to food availability. This suggests that EGL-10 and EAT-16 may set baseline levels of G protein signaling, while RGS-1 and RGS-2 redundantly alter signaling after re-feeding to cause appropriate behavioral changes. Several lines of evidence suggest that RGS-1 and RGS-2 induce behavioral change by negatively regulating GOA-1. First,
goa-1 null mutants completely fail to alter egg-laying behavior when food conditions are changed, indicating that GOA-1 is a key component in directing behavioral changes. Second, overexpression of
rgs-1 or
rgs-2 mimics, to different degrees, the
goa-1 loss-of-function phenotype. Third, some GOA-1 expressing neurons also express RGS-1 and RGS-2. Lastly, purified RGS-1 and RGS-2 proteins both stimulate the GTPase activity of purified GOA-1. We propose that C. elegans utilizes three RGS proteins to regulate different aspects of GOA-1 signaling: EGL-10 sets the baseline signaling level, while RGS-1 and RGS-2 redundantly inhibit GOA-1 to rapidly induce egg-laying behavior in response to feeding after food deprivation. Koelle, M.R. and Horvitz, H.R. (1996) Cell 84, 115-125. Hajdu-Cronin YM, Chen WJ, Patikoglou G, Koelle MR, Sternberg PW. (1999) Genes Dev. 13, 1780-93.