{
  "abstract": "Mutations in Syntaxin11 (STX11), a Q-SNARE, result in a fatal immune disorder known as familial hemophagocytic lymphohistiocytosis 4 (FHLH4) in human patients. A key diagnostic feature of FHLH4 is defective T and natural killer cell cytotoxicity. Here, we show that STX11 directly binds and regulates Orai1, the pore-forming subunit of calcium release-activated calcium (CRAC) channels. CRAC channels enable store-operated calcium entry (SOCE) from the extracellular space and are crucial for granule exocytosis and nuclear factor of activated T cells (NFAT)-dependent gene expression in activated lymphocytes. STX11 depletion strongly inhibited SOCE, CRAC currents, NFAT activation, interleukin-2 gene expression, and degranulation in FHLH4 patient T lymphocytes and cell lines without affecting membrane trafficking. Remarkably, defects of cytolytic granule exocytosis, as well as interleukin-2 expression, could be reversed by ionomycin in patient T lymphocytes, and a constitutively active, H134S, mutant of Orai1 rescued calcium entry in STX11-depleted cells. Further analyses showed that STX11 'primes' Orai1 for optimal on-site multimeric assembly, which was Stim independent but required for gating. Priming of ion channel pore subunits is, therefore, a primary function of specific SNAREs which may have preceded their role in membrane trafficking and vesicle fusion.",
  "abstract_shown": true,
  "affiliations": [
    "Tata Institute of Fundamental Research, Hyderabad, India.",
    "National Centre for Biological Sciences, Bangalore, India.",
    "Northwestern University, Feinberg School of Medicine, Chicago, United States.",
    "Institute for Immunodeficiency, University of Freiburg, Freiburg im Breisgau, Germany.",
    "Institute for Transfusion Medicine and Gene Therapy, University of Freiburg, Freiburg im Breisgau, Germany.",
    "Dr. Shahrooei Lab, Tehran, Iran."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sritama Datta"
    },
    {
      "affs": [
        0
      ],
      "name": "Abhikarsh Gupta"
    },
    {
      "affs": [
        0
      ],
      "name": "Kunal M Jagetiya"
    },
    {
      "affs": [
        0
      ],
      "name": "Resmi Bera"
    },
    {
      "affs": [
        1
      ],
      "name": "Vikas R Tiwari"
    },
    {
      "affs": [
        2
      ],
      "name": "Megumi Yamashita"
    },
    {
      "affs": [
        0
      ],
      "name": "Atharva R Yande"
    },
    {
      "affs": [
        0
      ],
      "name": "Abdul Rishad"
    },
    {
      "affs": [
        0
      ],
      "name": "Vishal Malik"
    },
    {
      "affs": [
        0
      ],
      "name": "Sreejith Raran-Kurussi"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Sandra Ammann"
    },
    {
      "affs": [
        5
      ],
      "name": "Mohammad Shahrooei"
    },
    {
      "affs": [
        0
      ],
      "name": "Kalyaneswar Mandal"
    },
    {
      "affs": [
        1
      ],
      "name": "Ramanathan Sowdhamini"
    },
    {
      "affs": [
        2
      ],
      "name": "Murali Prakriya",
      "orcid": "0000-0003-0781-4480"
    },
    {
      "affs": [
        0
      ],
      "name": "Adish Dani",
      "orcid": "0000-0002-5491-7709"
    },
    {
      "affs": [
        0
      ],
      "name": "Monika Vig",
      "orcid": "0000-0002-4770-8853"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6p42as13amc0z.bib",
  "cited_by": 0,
  "doi": "10.7554/elife.111335",
  "fulltext_url": "https://europepmc.org/articles/PMC13679927",
  "id": "6p42as13amc0z",
  "issns": [
    "2050-084X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42895167",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2809|Ion Channels and Receptors"
    ]
  ],
  "openalex": "W7162100970",
  "pdf_url": "https://europepmc.org/articles/PMC13679927?pdf=render",
  "pmcid": "PMC13679927",
  "pmid": "42895167",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6p42as13amc0z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42895167",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42895167"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2809|Ion Channels and Receptors",
      "subfield": "neuroscience"
    }
  ],
  "title": "Syntaxin11 deficiency inhibits CRAC channel priming to suppress cytotoxicity and gene expression in T lymphocytes independent of membrane trafficking.",
  "title_text": "Syntaxin11 deficiency inhibits CRAC channel priming to suppress cytotoxicity and gene expression in T lymphocytes independent of membrane trafficking.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/6p42as13amc0z",
  "venue": "ELife",
  "versions": []
}