RRC ID 51351
Author Topalidou I, Chen PA, Cooper K, Watanabe S, Jorgensen EM, Ailion M.
Title The NCA-1 and NCA-2 Ion Channels Function Downstream of Gq and Rho To Regulate Locomotion in Caenorhabditis elegans.
Journal Genetics
Abstract The heterotrimeric G protein Gq positively regulates neuronal activity and synaptic transmission. Previously, the Rho guanine nucleotide exchange factor Trio was identified as a direct effector of Gq that acts in parallel to the canonical Gq effector phospholipase C. Here, we examine how Trio and Rho act to stimulate neuronal activity downstream of Gq 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 Gq-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 Gq 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 Gq-Rho signaling in C. elegans.
Volume 206(1)
Pages 265-282
Published 2017-5
DOI 10.1534/genetics.116.198820
PII genetics.116.198820
PMID 28325749
PMC PMC5419474
MeSH Acetylcholine / genetics Acetylcholine / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics* GTP-Binding Protein alpha Subunits, Gq-G11 / genetics* Ion Channels / genetics* Locomotion / genetics* Locomotion / physiology Mutation Nerve Tissue Proteins / genetics Neurons / physiology Signal Transduction / genetics Synaptic Transmission / genetics
IF 4.075
Resource
C.elegans tm3622 tm3631