The NCA-1 and NCA-2 ion channels function downstream of Gq and Rho to regulate locomotion inC. elegans

The heterotrimeric G protein G q positively regulates neuronal activity and synaptic transmission. Previously, the Rho guanine nucleotide exchange factor Trio was identified as a direct effector of G q that acts in parallel to the canonical G q effector phospholipase C. Here we examine how Trio and Rho act to stimulate neuronal activity downstream of G q in the nematode Caenorhabditis elegans . Through two forward genetic screens, we identify the cation channels NCA-1 and NCA-2, orthologs of mammalian NALCN, as downstream targets of the G q /Rho pathway. By performing genetic epistasis analysis using dominant activating mutations and recessive loss-of-function mutations in the members of this pathway, we show that NCA-1 and NCA-2 act downstream of G q in a linear pathway. Through cell-specific rescue experiments, we show that function of these channels in head acetylcholine neurons is sufficient for normal locomotion in C. elegans . Our results suggest that NCA-1 and NCA-2 are physiologically relevant targets of neuronal G q -Rho signaling in C. elegans .