Distinct unfolded protein responses mitigate or mediate effects of nonlethal deprivation of C. elegans sleep in...

Disrupting sleep during development leads to lasting deficits in chordates and arthropods. To address lasting impacts of sleep deprivation in Caenorhabditis elegans, we established a nonlethal deprivation protocol.

Deprivation triggered protective insulin-like signaling and two unfolded protein responses (UPRs): the mitochondrial (UPR^mt) and the endoplasmic reticulum (UPR^ER) responses. While the latter is known to be triggered by sleep deprivation in rodent and insect brains, the former was not strongly associated with sleep deprivation previously. We show that deprivation results in a feeding defect when the UPR^mt is deficient and in UPR^ER-dependent germ cell apoptosis. In addition, when the UPR^ER is deficient, deprivation causes excess twitching in vulval muscles, mirroring a trend caused by loss of egg-laying command neurons.

These data show that nonlethal deprivation of C. elegans sleep causes proteotoxic stress. Unless mitigated, distinct types of deprivation-induced proteotoxicity can lead to anatomically and genetically separable lasting defects. The relative importance of different UPRs post-deprivation likely reflects functional, developmental, and genetic differences between the respective tissues and circuits.