{
  "abstract": "Extracellular vesicles (EVs) are key mediators of intercellular communication with emerging therapeutic potential. Small EVs (~50-150 nm) released from skeletal muscle (SkM) following exercise improve insulin sensitivity and glucose tolerance in animal models, yet the molecular mechanisms governing their secretion remain poorly understood. Ca2+ signaling has been shown to regulate numerous membrane trafficking events ranging from vesicle transport, membrane repair, and exocytosis of cellular cargo. We investigated how Ca2+ signaling influences the intracellular trafficking and membrane delivery mechanisms necessary for EV release using an in vitro SkM cell model. We found that elevated intracellular Ca2+ stimulates EV secretion through a mechanism requiring activity of the octameric exocyst complex. Using proximity ligation assays, co-immunoprecipitation, structural modeling and proximity-dependent proteomics, we identified dynamic coordination between the exocyst complex and the small GTPase, Rab27a, during Ca2+-stimulated EV release. We found this coordination is modulated by Ca2+ signaling and perturbation of exocyst function. We then used direct binding assays to provide a structural basis for the proximity observed between GTP and GDP-loaded Rab27a and exocyst subunits. Additionally, proximity-dependent proteomics revealed that Ca2+ stimulation promoted the association of specific exocyst subunits with GTP-competent Rab27a, suggesting a nucleotide-state-dependent organization of this trafficking interface in living cells. Finally, we adapted a real-time reporter of EV exocytosis in SkM cells and identified Ca2+-responsive kinases that modulate EV secretion. Collectively, our findings support a model in which Ca2+ signaling reorganizes interactions between Rab27a and the exocyst to promote intracellular trafficking necessary for EV secretion in skeletal muscle cells.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "T. Nelson Luke",
      "orcid": "0000-0003-2851-6239"
    },
    {
      "name": "Jeremy Boulestreau",
      "orcid": "0000-0002-7231-2084"
    },
    {
      "name": "Noemi Polgar",
      "orcid": "0000-0002-8400-162X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/24n11hdxwrsxm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.761013",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761013v1.full",
  "id": "24n11hdxwrsxm",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761013v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7223463514",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761013v1.full.pdf",
  "pmcid": "PMC13738710",
  "pmid": "42995992",
  "published": "2026-10-22",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/24n11hdxwrsxm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:31Z",
      "native_id": "10.64898/2026.10.22.761013",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.22.761013v1"
    },
    {
      "first_seen": "2026-11-09T12:23:39Z",
      "native_id": "PMC13738710",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.22.761013"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Calcium signaling recruits Rab27a and the exocyst complex to promote small extracellular vesicle release in skeletal muscle cells",
  "title_text": "Calcium signaling recruits Rab27a and the exocyst complex to promote small extracellular vesicle release in skeletal muscle cells",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:39Z",
  "url": "https://research.draconitic.com/paper/24n11hdxwrsxm",
  "venue": "bioRxiv",
  "versions": []
}