The sleep state is widely observed in animals. The molecular mechanisms underlying sleep regulation, however, remain largely unclear. In the nematode Caenorhabditis elegans, developmentally timed sleep (DTS) and stress-induced sleep (SIS) are 2 types of quiescent behaviors that fulfill the definition of sleep and share conserved sleep-regulating molecules with mammals. To identify novel sleep-regulating molecules, we conducted an unbiased forward genetic screen based on DTS phenotypes. We isolated 2 mutants,
rem8 and
rem10, that exhibited significantly disrupted DTS and SIS. The causal gene of the abnormal sleep phenotypes in both mutants was mapped to
dgk-1, which encodes diacylglycerol kinase. Perhaps due to the diminished SIS,
dgk-1 mutant worms exhibited decreased survival following exposure to a noxious stimulus. Pan-neuronal and/or cholinergic expression of
dgk-1 partly rescued the
dgk-1 mutant defects in DTS, SIS, and post-stress survival. Moreover, we revealed that
pkc-1/nPKC participates in sleep regulation and counteracts the effect of
dgk-1; the reduced DTS, SIS, and post-stress survival rate were partly suppressed in the
pkc-1;
dgk-1 double mutant compared with the
dgk-1 single mutant. Excessive sleep observed in the
pkc-1 mutant was also suppressed in the
pkc-1;
dgk-1 double mutant, implying that
dgk-1 has a complicated mode of action. Our findings indicate that neuronal DGK-1 is essential for normal sleep and that the counterbalance between DGK-1 and PKC-1 is crucial for regulating sleep and mitigating post-stress damage.