Calcium/calmodulin-dependent protein kinase II regulates Caenorhabditis elegans locomotion in concert with a G(o)/G(q) signaling network

Caenorhabditis elegans locomotion is a complex behavior generated by a defi ned set of motor neurons and interneurons. Genetic analysis shows that UNC- 43, the C. elegans Ca2+/calmodulin protein kinase II (CaMKII), controls loc omotion rate. Elevated UNC-43 activity, from a gain-of-function mutation, c auses severely lethargic locomotion, presumably by inappropriate phosphoryl ation of targets. In a genetic screen for suppressors of this phenotype, we identified multiple alleles of four genes in a G(o)/G(q) G-protein signali ng network, which has been shown to regulate synaptic activity via diacylgl ycerol. Mutations in goa-1, dgk-1, eat-16, or eat-II strongly or completely suppressed unc-43(gf) lethargy, but affected other mutants with reduced lo comotion only weakly. We conclude that CaMKII and G(o)/G(q) pathway's act i n concert to regulate synaptic activity, perhaps through a direct interacti on between CaMKII and G(o).