RESUMEN
Sleep is conserved from invertebrates to vertebrates, and is tightly regulated in a homeostatic manner. The molecular and cellular mechanisms that determine the amount of rapid eye movement sleep (REMS) and non-REMS (NREMS) remain unknown. Here we identify two dominant mutations that affect sleep and wakefulness by using an electroencephalogram/electromyogram-based screen of randomly mutagenized mice. A splicing mutation in the Sik3 protein kinase gene causes a profound decrease in total wake time, owing to an increase in inherent sleep need. Sleep deprivation affects phosphorylation of regulatory sites on the kinase, suggesting a role for SIK3 in the homeostatic regulation of sleep amount. Sik3 orthologues also regulate sleep in fruitflies and roundworms. A missense, gain-of-function mutation in the sodium leak channel NALCN reduces the total amount and episode duration of REMS, apparently by increasing the excitability of REMS-inhibiting neurons. Our results substantiate the use of a forward-genetics approach for studying sleep behaviours in mice, and demonstrate the role of SIK3 and NALCN in regulating the amount of NREMS and REMS, respectively.
Asunto(s)
Canales Iónicos/genética , Mutagénesis , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas Serina-Treonina Quinasas/genética , Sueño/genética , Sueño/fisiología , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Secuencia Conservada , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Electroencefalografía , Electromiografía , Homeostasis/genética , Canales Iónicos/química , Canales Iónicos/metabolismo , Proteínas de la Membrana , Ratones , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/metabolismo , Empalme del ARN/genética , Distribución Aleatoria , Privación de Sueño , Sueño REM/genética , Sueño REM/fisiología , Factores de Tiempo , Vigilia/genética , Vigilia/fisiologíaRESUMEN
Sour citrus are prized for their flavor and fragrance. This work identified the components of the peel oil of Hetsuka-daidai (Citrus sp. hetsukadaidai), a special sour citrus that is native to the southern part of the Osumi peninsula, Kagoshima, Japan. These compounds were compared to those identified from the peels of six other major sour citrus: lime (Citrus latifolia), lemon (Citrus limon), Yuzu (Citrus junos), Kabusu (Citrus aurantium), Kabosu (Citrus sphaerocarpa), and Sudachi (Citrus sudachi). Peel oil contents were analyzed for the duration of four months during harvest season to investigate the differences in peel oil/fragrance during ripening. These results could facilitate the development of preferred flavor and scent profiles using local species.