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The study shows distinct isoforms of GEF-H1 (mouse Arhgef2-207; human ARHGEF2-219) localize to adherens junctions via Nectin-3 and Afadin. Conditional deletion of Arhgef2-207 induces compensatory Arhgef2-201 expression, barrier loss, autophagy activation, and small-intestinal inflammation. In human organoids, Listeria selectively targets ARHGEF2-219, triggers an isoform switch to ARHGEF2-201, and induces autophagy through STING/LC3, coinciding with polarity disruption and Na+/K+-ATPase loss.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/arhgef2-isoform-switching-couples-intestinal-epithelial-barrier-function-with-autophagic-response-to-pathogens/454490/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/arhgef2-isoform-switching-couples-intestinal-epithelial-barrier-function-with-autophagic-response-to-pathogens/454490.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn Holloway","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What isoforms of GEF-H1 are implicated in epithelial junction localization?","Question",{"text":112,"@type":113},"Distinct isoforms of GEF-H1 localize to adherens junctions: mouse Arhgef2-207 and human ARHGEF2-219. Their localization depends on interactions with Nectin-3 and the cytoskeletal scaffold Afadin.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What happens when Arhgef2-207 is conditionally deleted in intestinal epithelium?",{"text":117,"@type":113},"Conditional deletion of Arhgef2-207 induces compensatory expression of a shorter isoform, Arhgef2-201. This leads to loss of barrier integrity, activation of autophagy, and small-intestinal inflammation.",{"name":119,"@type":110,"acceptedAnswer":120},"How does Listeria monocytogenes trigger autophagy in human intestinal organoids?",{"text":121,"@type":113},"Listeria infection selectively targets the junction-associated ARHGEF2-219 isoform, causing an isoform switch to ARHGEF2-201. The switch induces autophagy through STING and LC3, alongside loss of epithelial polarity and Na+/K+-ATPase.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},454490,1791214961,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","UT Southwestern Medical Center [https://orcid.org/0000-0001-8283-644X](https://orcid.org/0000-0001-8283-644X)  \nUniversity of Texas Southwestern Medical Center  \nUniversity of Texas Southwestern Medical Center [https://orcid.org/0009-0002-2473-6074](https://orcid.org/0009-0002-2473-6074)  \nDivision of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center  \nUT Southwestern Medical Center [https://orcid.org/0009-0000-1470-1324](https://orcid.org/0009-0000-1470-1324)  \nUT Southwestern Medical Center [https://orcid.org/0000-0002-6072-2377](https://orcid.org/0000-0002-6072-2377)  \nUT Southwestern Medical Center  \nUniversity of Texas Southwestern Medical Center  \nUT Southwestern Medical Center  \nUT Southwestern Medical Center  \nUniversity of Texas Southwestern Medical Center [https://orcid.org/0000-0001-5815-4457](https://orcid.org/0000-0001-5815-4457)  \nUniversity of Texas Southwestern Medical Center  \nThe University of Texas Southwestern Medical Center [https://orcid.org/0000-0003-4341-6367](https://orcid.org/0000-0003-4341-6367)  \nUT Southwestern Medical Center  \nUT Southwestern Medical Center [https://orcid.org/0000-0002-4943-0170](https://orcid.org/0000-0002-4943-0170)  \n12. Division of Digestive and Liver Diseases, Center for Human Nutrition, University of Texas Southwestern Medical Center  \nUT Southwestern Medical Center  \nDecember 11th, 2025  \n [https://doi.org/10.21203/rs.3.rs-8252764/v1](https://doi.org/10.21203/rs.3.rs-8252764/v1)  \n 􀁱 􀅏 This work is licensed under a Creative Commons Attribution 4.0 International License.  \nRead Full License  \n There is  Competing Interest.  \n1 ARHGEF2 Isoform Switching Couples Intestinal Epithelial Barrier Function with  \n2 Autophagic Response to Pathogens.  \n3 Shuyuan Chen 1†, Alka Diwaker †1, Xi Li 1, Abdulmajeed Salamah 1,5, Lei Guo2, Neethu S. Alex 1, 4 Ashutosh Shukla 1, Mary-Joe Touma 1, Yassin EL-Najjar1, Lin Xu 2, Jianyi Yin 1, Ezra Burstein 1, 5 Marcel Mettlen 3, Andrew Lemoff 4, Suraj Patel 1, Josephine Ni 1 and Hans-Christian Reinecker 1,5, 6 6, 7*  \n7 1 Department of Medicine, Division of Digestive and Liver Diseases, University of Texas  \n8 Southwestern Medical Center, 5959 Harry Hines Boulevard, Dallas, Texas 75390, United States  \n9 2 Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health,  \n10 University of Texas Southwestern Medical Center, Texas 75390, United States  \n11 3 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX  \n12 75390, United States  \n13 4 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX  \n14 75390, United States  \n15 5 Department of Immunology, University of Texas Southwestern Medical Center, 5959 Harry  \n16 Hines Boulevard, Dallas, Texas 75390, United States  \n17 6 Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, 5959  \n18 Harry Hines Boulevard, Dallas, Texas 75390, United States  \n19 7 Simmons Cancer Center, University of Texas Southwestern Medical Center, 5959 Harry Hines  \n20 Boulevard, Dallas, Texas 75390, United States  \n21 *[Corresponding author:](Corresponding author: hans-christian.reinecker@utsouthwestern.edu)[ hans-christian.reinecker@utsouthwestern.edu](Corresponding author: hans-christian.reinecker@utsouthwestern.edu)  \n[22](22) †these authors contributed equally.  \n24 Abstract  \n25 Maintenance of intestinal epithelial integrity is essential for host defence, yet how epithelial  \n26 junctional scaffolds connect to antimicrobial autophagy remains unclear. Here we show that  \n27 distinct isoforms of the guanine nucleotide exchange factor GEF-H1 (mouse Arhgef2-207; human 28 ARHGEF2-219) localize to adherens junctions in polarized intestinal epithelial cells through  \n29 interaction with the adhesion molecule Nectin-3 and the cytoskeletal scaffold Afadin. Conditional  \n30 deletion of Arhgef2-207 in the intestinal epithelium induces compensatory","cbCaipt1GwZtGSLJ","https://ap.wps.com/l/cbCaipt1GwZtGSLJ","pdf",1848915,46,"English","# Abstract\n# Introduction","[{\"question\":\"What isoforms of GEF-H1 are implicated in epithelial junction localization?\",\"answer\":\"Distinct isoforms of GEF-H1 localize to adherens junctions: mouse Arhgef2-207 and human ARHGEF2-219. Their localization depends on interactions with Nectin-3 and the cytoskeletal scaffold Afadin.\"},{\"question\":\"What happens when Arhgef2-207 is conditionally deleted in intestinal epithelium?\",\"answer\":\"Conditional deletion of Arhgef2-207 induces compensatory expression of a shorter isoform, Arhgef2-201. This leads to loss of barrier integrity, activation of autophagy, and small-intestinal inflammation.\"},{\"question\":\"How does Listeria monocytogenes trigger autophagy in human intestinal organoids?\",\"answer\":\"Listeria infection selectively targets the junction-associated ARHGEF2-219 isoform, causing an isoform switch to ARHGEF2-201. The switch induces autophagy through STING and LC3, alongside loss of epithelial polarity and Na+/K+-ATPase.\"}]","ARHGEF2 Isoform Switching Couples Intestinal Epithelial Barrier Function with Autophagic Response to Pathogens | PDF",1790740789,116]