{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:36:20Z","timestamp":1788543380766,"version":"build-2803163510"},"reference-count":81,"publisher":"The Company of Biologists","issue":"24","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["F31-GM130112"],"award-info":[{"award-number":["F31-GM130112"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DC000097"],"award-info":[{"award-number":["DC000097"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-HL158979"],"award-info":[{"award-number":["R01-HL158979"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Emory University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Tight junctions regulate epithelial barrier function and have been shown to be influenced by multiple classes of proteins. Apical integrins have been identified as potential regulators of epithelial barrier function; however, only indirect approaches have been used to measure integrin regulation of the epithelial barrier. Here, we used polymeric nanowires conjugated with anti-integrin \u03b21 antibodies to specifically target apically localized integrins in either their closed or open conformation. Barrier regulation by apical integrins was found to be conformation specific. Nanowires targeting integrins in the closed conformation increased epithelial permeability and caused zonula occludens-1 (ZO-1, also known as TJP1) to change from a linear to a ruffled morphology. Claudin-2 and claudin-4 colocalized with ZO-1 and were also ruffled; however, claudin-1 and claudin-7 remained linear. Ruffling was dependent on myosin light chain kinases (MLCKs) and Rho kinases (ROCKs). Conversely, targeting integrins in the open conformation decreased epithelial permeability and made junctions more linearized. Anti-integrin \u03b21 nanowires differentially affected actin and talin (analyzed using pan-talin antibodies), depending on whether they contained activating or inhibitory antibodies. Thus, apical integrins can act as a conformation-sensitive switch that regulates epithelial barrier function.<\/jats:p>","DOI":"10.1242\/jcs.263580","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T08:24:11Z","timestamp":1731918251000},"source":"Crossref","is-referenced-by-count":7,"title":["Apical integrins as a switchable target to regulate the epithelial barrier"],"prefix":"10.1242","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-1162","authenticated-orcid":false,"given":"Raven J.","family":"Peterson","sequence":"first","affiliation":[{"name":"Emory University School of Medicine 1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine , , Atlanta, GA 30322 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan C.","family":"Reed","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine 1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine , , Atlanta, GA 30322 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-1388","authenticated-orcid":false,"given":"Colin R.","family":"Zamecnik","sequence":"additional","affiliation":[{"name":"University of California San Francisco 2 Department of Bioengineering and Therapeutic Sciences , , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9097-4754","authenticated-orcid":false,"given":"Marwa A.","family":"Sallam","sequence":"additional","affiliation":[{"name":", Brown University 3 School of Engineering , Providence, RI 02912 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0411-1755","authenticated-orcid":false,"given":"Joel A.","family":"Finbloom","sequence":"additional","affiliation":[{"name":"University of California San Francisco 2 Department of Bioengineering and Therapeutic Sciences , , San Francisco, CA 94158 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine 1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine , , Atlanta, GA 30322 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5907-3421","authenticated-orcid":false,"given":"Joshua M.","family":"Levy","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine 4 Department of Otolaryngology , , Atlanta, GA 30322 ,","place":["USA"]},{"name":"National Institute on Deafness and Other Communication Disorders, National Institutes of Health 5 , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8946-8694","authenticated-orcid":false,"given":"Aekkacha","family":"Moonwiriyakit","sequence":"additional","affiliation":[{"name":"Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University 6 , Bang Phli, Samut Prakan, 10540 ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3409-9208","authenticated-orcid":false,"given":"Tejal A.","family":"Desai","sequence":"additional","affiliation":[{"name":"University of California San Francisco 2 Department of Bioengineering and Therapeutic Sciences , , San Francisco, CA 94158 ,","place":["USA"]},{"name":", Brown University 3 School of Engineering , Providence, RI 02912 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5422-5614","authenticated-orcid":false,"given":"Michael","family":"Koval","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine 1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine , , Atlanta, GA 30322 ,","place":["USA"]},{"name":"Emory University School of Medicine 7 Department of Cell Biology , , Atlanta, GA 30322 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"2024122014020966600_JCS263580C1","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1016\/j.neuron.2022.02.017","article-title":"Pericyte-to-endothelial cell signaling via vitronectin-integrin regulates blood-CNS barrier","volume":"110","author":"Ayloo","year":"2022","journal-title":"Neuron"},{"key":"2024122014020966600_JCS263580C2","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1021\/bc200148v","article-title":"Tunable degradation of maleimide-thiol adducts in reducing environments","volume":"22","author":"Baldwin","year":"2011","journal-title":"Bioconjug. 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