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C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides

Nath, Ravi D. and Chow, Elly S. and Wang, Han and Schwarz, Erich M. and Sternberg, Paul W. (2016) C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides. Current Biology, 26 (18). pp. 2446-2455. ISSN 0960-9822. PMCID PMC5694219. http://resolver.caltech.edu/CaltechAUTHORS:20160818-085530875

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Abstract

The genetic basis of sleep regulation remains poorly understood. In C. elegans, cellular stress induces sleep through epidermal growth factor (EGF)-dependent activation of the EGF receptor in the ALA neuron. The downstream mechanism by which this neuron promotes sleep is unknown. Single-cell RNA sequencing of ALA reveals that the most highly expressed, ALA-enriched genes encode neuropeptides. Here we have systematically investigated the four most highly enriched neuropeptides: flp-7, nlp-8, flp-24, and flp-13. When individually removed by null mutation, these peptides had little or no effect on stress-induced sleep. However, stress-induced sleep was abolished in nlp-8; flp-24; flp-13 triple-mutant animals, indicating that these neuropeptides work collectively in controlling stress-induced sleep. We tested the effect of overexpression of these neuropeptide genes on five behaviors modulated during sleep—pharyngeal pumping, defecation, locomotion, head movement, and avoidance response to an aversive stimulus—and we found that, if individually overexpressed, each of three neuropeptides (nlp-8, flp-24, or flp-13) induced a different suite of sleep-associated behaviors. These overexpression results raise the possibility that individual components of sleep might be specified by individual neuropeptides or combinations of neuropeptides.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.cub.2016.07.048DOIArticle
http://www.sciencedirect.com/science/article/pii/S0960982216308417PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694219PubMed CentralArticle
ORCID:
AuthorORCID
Sternberg, Paul W.0000-0002-7699-0173
Additional Information:© 2016 Elsevier Ltd. Received 14 April 2016, Revised 15 June 2016, Accepted 19 July 2016, Available online 18 August 2016, Published: August 18, 2016. We thank the Caenorhabditis Genetics Center (NIH P40OD010440) and S. Mitani for strains, WormBase for bioinformatics support, Gladys Medina for technical support, the Millard and Muriel Jacobs Genetics and Genomics Laboratory for sequencing, and members of our laboratories for discussions. We thank Cheryl Van Buskirk for sharing unpublished observations and Dr. Daniel Lee, Dr. David Prober, Dr. John Bedbrook, Claire Bedbrook, Dr. Hillel Schwartz, and Dr. Mihoko Kato for comments and discussions. We thank Monica Savasta for generating graphics. This work was supported by the Howard Hughes Medical Institute(147-101), of which P.W.S. is an investigator, and NIH grant GM084389 to P.W.S. R.D.N. was supported by NIH grant T32GM007616. H.W. is supported by a Della Martin Postdoctoral Fellowship. The strain carrying the tm2427 allele is available through the National BioResource Project, subject to a materials transfer agreement. Author Contributions: E.S.C., E.M.S., R.D.N., and P.W.S. conceived the project. E.S.C. dissected ALA neurons and sequenced their amplified cDNA. E.M.S. performed the ALA transcriptome analysis. R.D.N., E.S.C., and H.W. performed C. elegans behavior experiments. E.S.C., H.W., and R.D.N. generated reagents. R.D.N., E.S.C., H.W., E.M.S., and P.W.S. wrote the paper. Accession Numbers: The accession number for the RNA-seq reads for the two pools of wild-type mid-L4 ALA neurons reported in this paper is NCBI Sequence Read Archive (SRA): SRP038903. The accession number for the RNA-seq reads for the two pools of whole C. elegans mixed-stage wild-type N2 larvae reused in this paper is SRA: SRP015688.
Funders:
Funding AgencyGrant Number
NIHP40OD010440
Millard and Muriel Jacobs Genetics and Genomics LaboratoryUNSPECIFIED
Howard Hughes Medical Institute (HHMI)147-101
NIHGM084389
NIH Predoctoral FellowshipT32GM007616
Della Martin Postdoctoral FellowshipUNSPECIFIED
Subject Keywords:sleep regulation; RFamides; neuropeptide modulation; single-neuron RNA-seq; genetic redundancy
PubMed Central ID:PMC5694219
Record Number:CaltechAUTHORS:20160818-085530875
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160818-085530875
Official Citation:Ravi D. Nath, Elly S. Chow, Han Wang, Erich M. Schwarz, Paul W. Sternberg, C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides, Current Biology, Volume 26, Issue 18, 26 September 2016, Pages 2446-2455, ISSN 0960-9822, http://dx.doi.org/10.1016/j.cub.2016.07.048. (http://www.sciencedirect.com/science/article/pii/S0960982216308417)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:69749
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:18 Aug 2016 17:10
Last Modified:20 Nov 2017 18:05

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