title: Role of Homer proteins in the maintenance of sleep-wake states.
abstract: Sleep is an evolutionarily conserved process that is linked to diurnal cycles and normal daytime wakefulness. Healthy sleep and wakefulness are integral to a healthy lifestyle; this occurs when an organism is able to maintain long bouts of both sleep and wake. Homer proteins, which function as adaptors for group 1 metabotropic glutamate receptors, have been implicated in genetic studies of sleep in both Drosophila and mouse. Drosophila express a single Homer gene product that is upregulated during sleep. By contrast, vertebrates express Homer as both constitutive and immediate early gene (H1a) forms, and H1a is up-regulated during wakefulness. Genetic deletion of Homer in Drosophila results in fragmented sleep and in failure to sustain long bouts of sleep, even under increased sleep drive. However, deletion of Homer1a in mouse results in failure to sustain long bouts of wakefulness. Further evidence for the role of Homer1a in the maintenance of wake comes from the CREB alpha delta mutant mouse, which displays a reduced wake phenotype similar to the Homer1a knockout and fails to up-regulate Homer1a upon sleep loss. Homer1a is a gene whose expression is induced by CREB. Sustained behaviors of the sleep/wake cycle are created by molecular pathways that are distinct from those for arousal or short bouts, and implicate an evolutionarily-conserved role for Homer in sustaining these behaviors.
authors.affiliation: Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. naidoo@mail.med.upenn.edu
authors.forename: Nirinjini
authors.initials: N
authors.lastname: Naidoo
authors.forename: Megan
authors.initials: M
authors.lastname: Ferber
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Galante
authors.forename: Blake
authors.initials: B
authors.lastname: McShane
authors.forename: Jia Hua
authors.initials: JH
authors.lastname: Hu
authors.forename: John
authors.initials: J
authors.lastname: Zimmerman
authors.forename: Greg
authors.initials: G
authors.lastname: Maislin
authors.forename: Jacqui
authors.initials: J
authors.lastname: Cater
authors.forename: Abraham
authors.initials: A
authors.lastname: Wyner
authors.forename: Paul
authors.initials: P
authors.lastname: Worley
authors.forename: Allan I
authors.initials: AI
authors.lastname: Pack
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001143:Arousal / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics; D004330:Drosophila; D000072233:Homer Scaffolding Proteins; D051379:Mice; D018345:Mice, Knockout; D012890:Sleep / Q000235:genetics*; D012892:Sleep Deprivation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D014851:Wakefulness / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606630:homer protein, Drosophila