{
  "abstract": "Neurexins are critical synaptic cell adhesion molecules that play many roles in modulating neurotransmitter release and synaptic function, and are high-confidence risk genes for neurodevelopmental conditions such as autism. Understanding the function of the neurexin superfamily has been challenging in mammalian systems that have 3 genes ( NRXN1-3 ) that encode 2-3 major isoforms, which undergo extensive alternative splicing and generate thousands of transcripts. In contrast to mammals, C. elegans has a single gene, nrx-1 , encoding only long α and short γ isoforms. Neurexins canonically regulate synapse morphology and function in a neuron- and context-specific manner, through mechanisms related to release of chemical neurotransmitters and receptors. Whether neurexins ( nrx-1 ) impact other secretory molecules such as neuropeptides (NPs) and NP containing dense-core vesicles (DCVs) is not well understood. Here, we report that loss of nrx-1 increases the release of multiple NPs from cholinergic motor neurons in C. elegans . Using tissue specific expression and degradation of endogenous NRX-1, we find that nrx-1 functions in NP release from cholinergic neurons in a cell-autonomous manner. We confirm that loss of nrx-1 impacts cholinergic active-zone number, but also find it regulates the clustering, distribution, and expression of the DCV protein, IDA-1 (PTPRN), and the DCV secretion regulator, UNC-31 (CADPS). We find that nrx-1 functions to maintain separation and juxtaposition of neurotransmitter and NP release sites and DCV localization. Loss of cholinergic excitation ( unc-17 ) or GABAergic inhibition ( unc-25 ) did not impact cholinergic NP release, but that the increased NP release upon loss of nrx-1 is dependent on the calcium channel unc-2 . We find that neurexins can regulate NP signaling, a novel mechanism to modify circuits and behaviors, and of potential importance for NRXN1 associated human conditions.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "Vina Tikiyani",
      "orcid": "0000-0001-8533-1885"
    },
    {
      "name": "Michael P. Hart",
      "orcid": "0000-0001-8865-3062"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6g993gem8n8xm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.31.748337",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13622485/",
  "id": "6g993gem8n8xm",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://doi.org/10.64898/2026.08.31.748337",
  "language": "en",
  "licence": "CC-BY-ND-4.0",
  "licence_label": "CC BY-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2804|Neuroscience and Neuropharmacology Research"
    ]
  ],
  "openalex": "W7208773894",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748337v1.full.pdf",
  "pmcid": "PMC13622485",
  "pmid": "42818522",
  "published": "2026-08-31",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/6g993gem8n8xm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:30Z",
      "native_id": "PMC13622485",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.08.31.748337"
    },
    {
      "first_seen": "2026-10-30T12:19:28Z",
      "native_id": "10.64898/2026.08.31.748337",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748337v3"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Neurexin mediates neuropeptide release from cholinergic motor neurons through dense-core vesicle localization",
  "title_text": "Neurexin mediates neuropeptide release from cholinergic motor neurons through dense-core vesicle localization",
  "type": "preprint",
  "updated_at": "2026-10-30T12:33:29Z",
  "url": "https://research.draconitic.com/paper/6g993gem8n8xm",
  "venue": "bioRxiv",
  "versions": []
}