Serotonin modulates circadian entrainment in Drosophila.
Entrainment of the Drosophila circadian clock to light involves the light-induced degradation of the clock protein timeless (TIM). We show here that this entrainment mechanism is inhibited by serotonin, acting through the Drosophila serotonin receptor 1B (d5-HT1B). d5-HT1B is expressed in clock neurons, and alterations of its levels affect molecular and behavioral responses of the clock to light. Effects of d5-HT1B are synergistic with a mutation in the circadian photoreceptor cryptochrome (CRY) and are mediated by SHAGGY (SGG), Drosophila glycogen synthase kinase 3beta (GSK3beta), which phosphorylates TIM. Levels of serotonin are decreased in flies maintained in extended constant darkness, suggesting that modulation of the clock by serotonin may vary under different environmental conditions. These data identify a molecular connection between serotonin signaling and the central clock component TIM and suggest a homeostatic mechanism for the regulation of circadian photosensitivity in Drosophila.
Howard Hughes Medical Institute, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA.
Quan
Q
Yuan
Fangju
F
Lin
Xiangzhong
X
Zheng
Amita
A
Sehgal
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D001923:Brain Chemistry; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015283:Citalopram / Q000494:pharmacology; D004330:Drosophila / Q000502:physiology*; D005473:Fluoxetine / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D007150:Immunohistochemistry; D008027:Light; D009154:Mutation / Q000502:physiology; D010766:Phosphorylation; D034622:RNA Interference; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D006916:5-Hydroxytryptophan; D015283:Citalopram; D005473:Fluoxetine; D038362:Glycogen Synthase Kinase 3; D044282:Receptor, Serotonin, 5-HT1A; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors