{
  "abstract": "Endoplasmic reticulum-plasma membrane (ER-PM) junctions coordinate Ca2+ signalling and nociceptor excitability during inflammation, but the molecular scaffold governing assembly of signalling complexes remains unclear. Here, we identify Extended Synaptotagmin-1 (Esyt1) as a key, dynamic regulator of inflammatory pain signalling. In nociceptive DRG neurons, Esyt1 is co-expressed with ANO1 and IP3R1. Time-resolved proximity ligation assays and super-resolution microscopy showed that bradykinin rapidly increased ANO1-Esyt1 nanoscale proximity, while IP3R1-Esyt1 interactions were dynamically reorganised during ANO1-IP3R1 complex formation. Esyt1 knockdown reduced bradykinin-evoked ANO1 activity, impaired store-operated Ca2+ entry (SOCE), decreased STIM1-Orai1 complex formation, and disrupted ER Ca2+ store refilling. Simultaneous imaging of Ca2+ dynamics and ANO1 activity demonstrated functional coupling between SOCE and ANO1 that required Esyt1. Furthermore, in-vivo Esyt1-knockdown significantly reduced bradykinin-induced nocifensive behaviour. Together, these findings identify Esyt1 as a Ca2+-responsive scaffold that organises ER-PM signalling nanodomains and promotes inflammatory pain signalling.",
  "abstract_shown": true,
  "affiliations": [
    "University of Leeds"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "C. Palfrey"
    },
    {
      "name": "J. Grayston"
    },
    {
      "name": "X. Zhang"
    },
    {
      "name": "Y. Gao"
    },
    {
      "name": "S. Figoli"
    },
    {
      "name": "L. Dougherty"
    },
    {
      "name": "Z. Chen"
    },
    {
      "name": "V. Prato"
    },
    {
      "name": "F. Jones"
    },
    {
      "name": "S. Milne"
    },
    {
      "name": "H. Gao"
    },
    {
      "name": "M. Shapiro"
    },
    {
      "name": "N. Gamper"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Shah"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9p3cjrebzk6xh.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.28.762450",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762450v1.full",
  "id": "9p3cjrebzk6xh",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762450v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762450v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9p3cjrebzk6xh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:23Z",
      "native_id": "10.64898/2026.10.28.762450",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762450v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Junctional Nanodomains Organised by Extended Synaptotagmin-1 Underlie Inflammatory Signalling in Sensory Neurons",
  "title_text": "Junctional Nanodomains Organised by Extended Synaptotagmin-1 Underlie Inflammatory Signalling in Sensory Neurons",
  "type": "preprint",
  "updated_at": "2026-10-31T00:20:43Z",
  "url": "https://research.draconitic.com/paper/9p3cjrebzk6xh",
  "venue": "bioRxiv",
  "versions": []
}