Stress response genes protect against lethal effects of sleep deprivation in Drosophila.
Sleep is controlled by two processes: a homeostatic drive that increases during waking and dissipates during sleep, and a circadian pacemaker that controls its timing. Although these two systems can operate independently, recent studies indicate a more intimate relationship. To study the interaction between homeostatic and circadian processes in Drosophila, we examined homeostasis in the canonical loss-of-function clock mutants period (per(01)), timeless (tim(01)), clock (Clk(jrk)) and cycle (cyc(01)). cyc(01) mutants showed a disproportionately large sleep rebound and died after 10 hours of sleep deprivation, although they were more resistant than other clock mutants to various stressors. Unlike other clock mutants, cyc(01) flies showed a reduced expression of heat-shock genes after sleep loss. However, activating heat-shock genes before sleep deprivation rescued cyc(01) flies from its lethal effects. Consistent with the protective effect of heat-shock genes, was the observation that flies carrying a mutation for the heat-shock protein Hsp83 (Hsp83(08445)) showed exaggerated homeostatic response and died after sleep deprivation. These data represent the first step in identifying the molecular mechanisms that constitute the sleep homeostat.
Shaw
Paul J
PJ
The Neurosciences Institute, 10640 John J. Hopkins Drive, San Diego, California 92121, USA.
Tononi
Giulio
G
Greenspan
Ralph J
RJ
Robinson
Donald F
DF
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003624:Darkness; D003681:Dehydration; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005260:Female; D005508:Food Deprivation; D005786:Gene Expression Regulation; D017344:Genes, Insect / Q000235:genetics*; D005804:Genes, Lethal / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics; D006706:Homeostasis; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008027:Light; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D056950:Period Circadian Proteins; D012890:Sleep / Q000235:genetics / Q000502:physiology; D012892:Sleep Deprivation / Q000235:genetics / Q000401:mortality* / Q000503:physiopathology*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014851:Wakefulness / Q000235:genetics / Q000502:physiology
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D015534:Trans-Activators; C089272:Hsp83 protein, Drosophila; C539040:PER protein, Drosophila; C112805:cyc protein, Drosophila; C096445:tim protein, Drosophila