The NCA-1 and NCA-2 Ion Channels Function Downstream of Gqand Rho To Regulate Locomotion inCaenorhabditis elegans.
The heterotrimeric G protein Gqpositively regulates neuronal activity and synaptic transmission. Previously, the Rho guanine nucleotide exchange factor Trio was identified as a direct effector of Gqthat acts in parallel to the canonical Gqeffector phospholipase C. Here, we examine how Trio and Rho act to stimulate neuronal activity downstream of Gqin the nematodeCaenorhabditis elegansThrough 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 Gqin a linear pathway. Through cell-specific rescue experiments, we show that function of these channels in head acetylcholine neurons is sufficient for normal locomotion inC. elegansOur results suggest that NCA-1 and NCA-2 are physiologically relevant targets of neuronal Gq-Rho signaling inC. elegans.
Department of Biochemistry, University of Washington, Seattle, Washington 98195.
Irini
I
Topalidou
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, Utah 84112.
Pin-An
PA
Chen
Department of Biochemistry, University of Washington, Seattle, Washington 98195.
Kirsten
K
Cooper
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, Utah 84112.
Shigeki
S
Watanabe
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, Utah 84112.
Erik M
EM
Jorgensen
Department of Biochemistry, University of Washington, Seattle, Washington 98195 mailion@uw.edu.
Michael
0000-0002-8070-1362
M
Ailion
D000109:Acetylcholine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics*; D007473:Ion Channels / Q000235:genetics*; D008124:Locomotion / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D007473:Ion Channels; C525142:NCA-2 protein, C elegans; D009419:Nerve Tissue Proteins; C525141:unc-77 protein, C elegans; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D000109:Acetylcholine
C. elegans; G protein; Gq signaling; NCA/NALCN ion channels; Rho small GTPase