G Protein-Coupled Receptor Kinase-2 (GRK-2) Controls Exploration Through Neuropeptide Signaling in Caenorhabditis Elegans
Animals alter their behavior in manners that depend on environmental conditions as well as their developmental and metabolic states. For example, C. elegans is quiescent during larval molts or during conditions of satiety. By contrast, worms enter an exploration state when removed from food. Sensory perception influences movement quiescence (defined as a lack of body movement), as well as the expression of additional locomotor states in C. elegans that are associated with increased or reduced locomotion activity, such as roaming (exploration behavior) and dwelling (local search). Here we find that movement quiescence is enhanced, and exploration behavior is reduced in G protein-coupled receptor kinase grk-2 mutant animals. grk-2 was previously shown to act in chemosensation, locomotion, and egg-laying behaviors. Using neuron-specific rescuing experiments, we show that GRK-2 acts in multiple ciliated chemosensory neurons to control exploration behavior. grk-2 acts in opposite ways from the cGMP-dependent protein kinase gene egl-4 to control movement quiescence and exploration behavior. Analysis of mutants with defects in ciliated sensory neurons indicates that grk-2 and the cilium-structure mutants act in the same pathway to control exploration behavior. We find that GRK-2 controls exploration behavior in an opposite manner from the neuropeptide receptor NPR-1 and the neuropeptides FLP-1 and FLP-18. Finally, we show that secretion of the FLP-1 neuropeptide is negatively regulated by GRK-2 and that overexpression of FLP-1 reduces exploration behavior. These results define neurons and molecular pathways that modulate movement quiescence and exploration behavior.
Davis, Kristen; Mitchell, Christo; Weissenfels, Olivia; Bai, Jihong; Raizen, David M.; Ailion, Michael; and Topalidou, Irini, "G Protein-Coupled Receptor Kinase-2 (GRK-2) Controls Exploration Through Neuropeptide Signaling in Caenorhabditis Elegans" (2023). Department of Neuroscience Faculty Papers. Paper 76.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
journal.pgen.1010613.s002.pdf (194 kB)
journal.pgen.1010613.s003.pdf (237 kB)
journal.pgen.1010613.s004.pdf (427 kB)
journal.pgen.1010613.s005.pdf (166 kB)
journal.pgen.1010613.s006.docx (23 kB)
journal.pgen.1010613.s007.docx (17 kB)
journal.pgen.1010613.s008.xlsx (117 kB)
This article is the author's final published version in PLoS Genetics, Volume 19, Issue 1, 2023, Article number e1010613.
The published version is available at https://doi.org/10.1371/journal.pgen.1010613. Copyright © 2023 Davis et al.