Figure 8.
Signaling through chloride channels and G-protein-coupled receptors regulates neurotransmitter release from the HSNs. Multiple signals converge on the HSNs and are integrated to set the level of serotonin release to control egg laying. Previous work indicates that the acetylcholine receptor GAR-2 and a serotonin autoreceptor are likely coupled to the Gαo-protein GOA-1 to inhibit neurotransmitter release from the HSNs. Here we demonstrate that KCC-2 acts in the HSNs to establish a chloride gradient necessary for neural inhibition through neurotransmitter-gated chloride channels, which are likely activated by GABA and/or tyramine, to regulate egg laying. Inhibition of HSN activity by EGL-47 depends on both Gαo and KCC-2, allowing genes involved in either process to be identified in the egl-47(dm) suppressor screen. Although EGL-47 is similar to G-protein-coupled receptors in primary structure, it has effects independent of Gαo, and the schematic indicates the possibility that it may activate chloride channels. KCC-2 and Gαo are also expressed in the egg-laying muscles, but both are only shown in the HSNs because this is the only site of function for these proteins in the control of egg laying as identified by cell-specific rescue experiments [this work and the one by Tanis et al. (2008)].