Antagonist actions of CMK-1/CaMKI and TAX-6/calcineurin along the <i>C. elegans</i> thermal avoidance circuit orchestrate adaptation of nociceptive response to repeated stimuli.

ABSTRACT: Thermal nociception in Caenorhabditis elegans is regulated by the Ca²⁺/calmodulin-dependent protein kinase CMK-1, but its downstream effectors have remained unclear. Here, we combined in vitro kinase assays with mass-spectrometry-based phosphoproteomics to identify hundreds of CMK-1 substrates, including the calcineurin A subunit TAX-6, phosphorylated within its conserved regulatory domain. Genetic and pharmacological analyses reveal multiple antagonistic interactions between CMK-1 and calcineurin signaling in modulating both naive thermal responsiveness and adaptation to repeated noxious stimuli. Cell-specific manipulations indicate that CMK-1 acts in AFD and ASER thermo-sensory neurons, while TAX-6 functions in FLP thermo-sensory neurons and downstream interneurons. Sin

SUBMITTER: Rudgalvyte M 

PROVIDER: S-EPMC12043318 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature