{
  "abstract": "Intestinal epithelial integrity is essential for host defense, yet how epithelial junctional scaffolds coordinate antimicrobial immunity remains unclear. We show that the long GEF-H1 isoforms (mouse Arhgef2-207; human ARHGEF2-219) localize to adherens junctions in polarized epithelial cells through interactions with actin and Nectin-3, whereas the shorter Arhgef2-201 isoform localizes to tight junctions. Conditional deletion of epithelial Arhgef2-207 induces Arhgef2-201 expression, disrupts barrier integrity, activates autophagy, and causes small-intestinal inflammation. In human intestinal organoids, Listeria monocytogenes selectively depletes junction-associated ARHGEF2-219, triggering a switch to ARHGEF2-201 and RhoA- and STING-mediated autophagic signaling. This transition coincides with loss of the Na⁺/K⁺-ATPase and epithelial polarity. Here we show that a pathogen-induced ARHGEF2 isoform switch links junctional perturbation to autophagic responses and immune activation, revealing a mechanism that couples barrier disruption to cell-intrinsic antimicrobial defense.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, 5959 Harry Hines Boulevard, Dallas, Texas USA",
    "Department of Immunology, University of Texas Southwestern Medical Center, 5959 Harry Hines Boulevard, Dallas, Texas USA",
    "Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health University of Texas Southwestern Medical Center, Dallas, Texas USA",
    "Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX USA",
    "Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX USA",
    "Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5959 Harry Hines Boulevard, Dallas, Texas USA",
    "Simmons Cancer Center, University of Texas Southwestern Medical Center, 5959 Harry Hines Boulevard, Dallas, Texas USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shuyuan Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Alka Diwaker",
      "orcid": "0009-0002-2473-6074"
    },
    {
      "affs": [
        0
      ],
      "name": "Xi Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Abdulmajeed Salamah",
      "orcid": "0009-0000-1470-1324"
    },
    {
      "affs": [
        2
      ],
      "name": "Lei Guo",
      "orcid": "0000-0002-6072-2377"
    },
    {
      "affs": [
        0
      ],
      "name": "Neethu S. Alex"
    },
    {
      "affs": [
        0
      ],
      "name": "Ashutosh Shukla"
    },
    {
      "affs": [
        0
      ],
      "name": "Mary-Joe Touma"
    },
    {
      "affs": [
        0
      ],
      "name": "Yassin EL-Najjar"
    },
    {
      "affs": [
        2
      ],
      "name": "Lin Xu",
      "orcid": "0000-0001-5815-4457"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianyi Yin"
    },
    {
      "affs": [
        0
      ],
      "name": "Ezra Burstein",
      "orcid": "0000-0003-4341-6367"
    },
    {
      "affs": [
        3
      ],
      "name": "Marcel Mettlen"
    },
    {
      "affs": [
        4
      ],
      "name": "Andrew Lemoff",
      "orcid": "0000-0002-4943-0170"
    },
    {
      "affs": [
        0
      ],
      "name": "Suraj Patel"
    },
    {
      "affs": [
        0
      ],
      "name": "Josephine Ni"
    },
    {
      "affs": [
        0,
        1,
        5,
        6
      ],
      "name": "Hans-Christian Reinecker",
      "orcid": "0000-0001-8283-644X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/632vj15febayh.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78030-w",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696713/",
  "id": "632vj15febayh",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-78030-w",
  "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",
      "Article"
    ],
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W4417221454",
  "pdf_url": "https://europepmc.org/articles/PMC13696713?pdf=render",
  "pmcid": "PMC13696713",
  "pmid": "42928288",
  "published": "2026-09-24",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/632vj15febayh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:01Z",
      "native_id": "PMC13696713",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-78030-w"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928288",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928288"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "ARHGEF2 isoform switching couples intestinal epithelial barrier function with autophagic host defense response to pathogens",
  "title_text": "ARHGEF2 isoform switching couples intestinal epithelial barrier function with autophagic host defense response to pathogens",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:00Z",
  "url": "https://research.draconitic.com/paper/632vj15febayh",
  "venue": "Nature Communications",
  "versions": []
}