Genome-Wide Screen for Genes Involved inCaenorhabditis elegansDevelopmentally Timed Sleep
| Autor: | Lukas L Skuja, Huiyan Huang, Dustin J Hayden, Chen-Tseh Zhu, Anne C. Hart |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Notch signaling pathway screen GPB-2 Context (language use) QH426-470 Biology 03 medical and health sciences Genetics sleep Heat shock Molecular Biology Genetics (clinical) Caenorhabditis elegans fungi Mutant Screen Report G protein biology.organism_classification Sleep in non-human animals GOA-1 Cell biology 030104 developmental biology C. elegans Signal transduction RGS Proteins Genetic screen |
| Zdroj: | G3: Genes, Genomes, Genetics, Vol 7, Iss 9, Pp 2907-2917 (2017) |
| ISSN: | 2160-1836 |
| DOI: | 10.1534/g3.117.300071 |
| Popis: | In Caenorhabditis elegans, Notch signaling regulates developmentally timed sleep during the transition from L4 larval stage to adulthood (L4/A) . To identify core sleep pathways and to find genes acting downstream of Notch signaling, we undertook the first genome-wide, classical genetic screen focused on C. elegans developmentally timed sleep. To increase screen efficiency, we first looked for mutations that suppressed inappropriate anachronistic sleep in adult hsp::osm-11 animals overexpressing the Notch coligand OSM-11 after heat shock. We retained suppressor lines that also had defects in L4/A developmentally timed sleep, without heat shock overexpression of the Notch coligand. Sixteen suppressor lines with defects in developmentally timed sleep were identified. One line carried a new allele of goa-1; loss of GOA-1 Gαo decreased C. elegans sleep. Another line carried a new allele of gpb-2, encoding a Gβ5 protein; Gβ5 proteins have not been previously implicated in sleep. In other scenarios, Gβ5 GPB-2 acts with regulators of G protein signaling (RGS proteins) EAT-16 and EGL-10 to terminate either EGL-30 Gαq signaling or GOA-1 Gαo signaling, respectively. We found that loss of Gβ5 GPB-2 or RGS EAT-16 decreased L4/A sleep. By contrast, EGL-10 loss had no impact. Instead, loss of RGS-1 and RGS-2 increased sleep. Combined, our results suggest that, in the context of L4/A sleep, GPB-2 predominantly acts with EAT-16 RGS to inhibit EGL-30 Gαq signaling. These results confirm the importance of G protein signaling in sleep and demonstrate that these core sleep pathways function genetically downstream of the Notch signaling events promoting sleep. |
| Databáze: | OpenAIRE |
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