RT Journal Article SR Electronic T1 The sek-1 p38 MAP kinase pathway regulates Gq signaling in C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 093252 DO 10.1101/093252 A1 Jill M. Hoyt A1 Samuel K. Wilson A1 Madhuri Kasa A1 Jeremy S. Rise A1 Irini Topalidou A1 Michael Ailion YR 2016 UL http://biorxiv.org/content/early/2016/12/13/093252.abstract AB 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 regulate both locomotion and Gq signaling. Furthermore, we find that sek-1 acts in mature neurons to regulate locomotion. Using genetic and behavioral approaches we demonstrate that other components of the p38 MAPK pathway also play a positive role in regulating 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.