{
  "abstract": "Neuropeptides modulate brain function by acting as ligands for a wide range of receptors. Systematic pharmacological screening efforts revealed extensive promiscuity in peptide-receptor pairs. However, the endogenous receptors and functions of promiscuous neuropeptides remain poorly understood. Here, we investigated how the Caenorhabditis elegans promiscuous RFamide-peptide FLP-14 and its receptors modulate a circuit for O2-evoked locomotory arousal. We show that FLP-14 peptides released from O2-sensing neurons and interneurons attenuate O2-evoked arousal by acting on 3 phylogenetically diverse G protein-coupled receptors (DMSR-3, FRPR-8, and NPR-40). Loss of each receptor individually confers strong hyperarousal by O2 comparable to the loss of flp-14. Distinct FLP-14 receptors have nonredundant roles in different target cells, including RID and RIM interneurons, that correlate antagonistically with locomotory arousal. Our results show that FLP-14 signaling requires coordinated modulation of multiple circuit nodes through distinct receptors in attenuating O2-evoked arousal. This promiscuous RFamide peptide network is reminiscent of monoaminergic neuromodulatory networks, which shape behavior through multiple receptors that differentially regulate distributed target neurons.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Nathan De Fruyt"
    },
    {
      "name": "Aleksandra Chudinova"
    },
    {
      "name": "Saurabh Thapliyal"
    },
    {
      "name": "Ellen Geens"
    },
    {
      "name": "Charline Roy"
    },
    {
      "name": "Elke Vandewyer"
    },
    {
      "name": "Sara Van Damme"
    },
    {
      "name": "Lucas Mergan"
    },
    {
      "name": "Isabel Beets",
      "orcid": "0000-0002-0968-4360"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0705q0pe3f26y.bib",
  "cited_by": 0,
  "doi": "10.1093/genetics/iyag188",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732711/",
  "id": "0705q0pe3f26y",
  "issns": [
    "0016-6731",
    "1943-2631"
  ],
  "landing_url": "https://doi.org/10.1093/genetics/iyag188",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/SCI01140"
    ],
    [
      "heading",
      "AcademicSubjects/SCI01180"
    ],
    [
      "heading",
      "Investigation"
    ],
    [
      "openalex",
      "2804|Neurobiology and Insect Physiology Research"
    ]
  ],
  "openalex": "W7169671444",
  "pdf_url": null,
  "pmcid": "PMC13732711",
  "pmid": "42470688",
  "published": "2026-07-18",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/0705q0pe3f26y.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:39Z",
      "native_id": "PMC13732711",
      "source": "pmc",
      "url": "https://doi.org/10.1093/genetics/iyag188"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Neurobiology and Insect Physiology Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Distinct receptors for a promiscuous RFamide neuropeptide co-regulate a distributed circuit for locomotory arousal in C. elegans",
  "title_text": "Distinct receptors for a promiscuous RFamide neuropeptide co-regulate a distributed circuit for locomotory arousal in C. elegans",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:39Z",
  "url": "https://research.draconitic.com/paper/0705q0pe3f26y",
  "venue": "Genetics",
  "versions": []
}