The NCA-1 and NCA-2 Ion Channels Function Downstream of G_q and Rho To Regulate Locomotion in Caenorhabditis 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.

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