A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis.
In the fruit fly, Drosophila melanogaster, rest shares features with mammalian sleep, including prolonged immobility, decreased sensory responsiveness and a homeostatic rebound after deprivation. To understand the molecular regulation of sleep-like rest, we investigated the involvement of a candidate gene, cAMP response-element binding protein (CREB). The duration of rest was inversely related to cAMP signaling and CREB activity. Acutely blocking CREB activity in transgenic flies did not affect the clock, but increased rest rebound. CREB mutants also had a prolonged and increased homeostatic rebound. In wild types, in vivo CREB activity increased after rest deprivation and remained elevated for a 72-hour recovery period. These data indicate that cAMP signaling has a non-circadian role in waking and rest homeostasis in Drosophila.
Hendricks
J C
JC
Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, 991 Maloney Building, 3600 Spruce St, Philadelphia, Pennsylvania, 19104 USA. jch@phl.vet.upenn.edu
Williams
J A
JA
Panckeri
K
K
Kirk
D
D
Tello
M
M
Yin
J C
JC
Sehgal
A
A
D000818:Animals; D030801:Animals, Genetically Modified; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D006706:Homeostasis; D006358:Hot Temperature; D008163:Luminescent Measurements; D009043:Motor Activity; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012146:Rest / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
C102181:CrebB protein, Drosophila; D017362:Cyclic AMP Response Element-Binding Protein; D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D000242:Cyclic AMP