Journal
G3-GENES GENOMES GENETICS
Volume 7, Issue 9, Pages 2979-2989Publisher
GENETICS SOCIETY AMERICA
DOI: 10.1534/g3.117.043273
Keywords
p38 MAPK pathway; Gq signaling; animal behavior; C. elegans
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Funding
- National Institutes of Health (NIH) Office of Research Infrastructure Programs [P40 OD010440]
- Public Health Service
- National Research Service from the National Institute of General Medical Sciences [T32GM007270]
- NIH [R00 MH082109]
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Gq is a heterotrimeric G protein that is widely expressed in neurons and regulates neuronal activity. To identify pathways regulating neuronal Gq signaling, we performed a forward genetic screen in Caenorhabditis elegans for suppressors of activated Gq. One of the suppressors is an allele of sek-1, which encodes a mitogen-activated protein kinase kinase (MAPKK) in the p38 MAPK pathway. Here, we show that sek-1 mutants have a slow locomotion rate and that sek-1 acts in acetylcholine neurons to modulate both locomotion rate and Gq signaling. Furthermore, we find that sek-1 acts in mature neurons to modulate locomotion. Using genetic and behavioral approaches, we demonstrate that other components of the p38 MAPK pathway also play a positive role in modulating locomotion and Gq signaling. Finally, we find that mutants in the SEK-1 p38 MAPK pathway partially suppress an activated mutant of the sodium leak channel, NCA-1/NALCN, a downstream target of Gq signaling. Our results suggest that the SEK-1 p38 pathway may modulate the output of Gq signaling through NCA-1(unc-77).
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