Genome-Wide screen for genes involved in Caenorhabditis elegans developmentally timed sleep

Huiyan Huang, Chen Tseh Zhu, Lukas L. Skuja, Dustin J. Hayden, Anne C. Hart

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2907-2917
Number of pages11
JournalG3: Genes, Genomes, Genetics
Volume7
Issue number9
DOIs
StatePublished - Sep 1 2017

Keywords

  • C. elegans
  • G protein
  • GOA-1
  • GPB-2
  • Mutant Screen
  • Report
  • Screen
  • Sleep

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