{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:33Z","timestamp":1785411393499,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,22]]},"group-title":"Cell Biology","reference-count":99,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["GM129312"],"award-info":[{"award-number":["GM129312"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["HL163611"],"award-info":[{"award-number":["HL163611"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["F30EY036267"],"award-info":[{"award-number":["F30EY036267"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Theory and Mathematics in Biology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Zonula adherens junctions (zAJ) are spatially proximal to tight junctions (TJ), in a superstructure known as the apical junctional complex (AJC). A key component of the AJC is a circumferential ring of filamentous (F)-actin, but how actomyosin contractility drives AJC structure and epithelial barrier function is incompletely understood. Here, we show that a central mechanosensitive component of zAJ, \u03b1-catenin (\u03b1-cat), undergoes force-dependent phosphorylation in an unstructured linker region. This modification in turn primes the \u03b1-cat mechanosensitive Middle-region for effector-binding. We credential Afadin, a multi-domain TJ\/AJ scaffold protein, as mechano-chemical binding partner of \u03b1-cat, identifying residues in \u03b1-cat required for this interaction. \u03b1-cat phosphorylation and Afadin-binding are required for their co-enrichment at zAJ and epithelial barrier function. A mouse model that prevents \u03b1-cat phosphorylation is particularly detrimental to post-natal brain development. These data support a stepwise model where \u03b1-cat integrates mechanical and chemical signals to progressively promote zAJ enrichment, effector recruitment and epithelial barrier function.<\/jats:p>","DOI":"10.1101\/2025.08.21.671625","type":"posted-content","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:20:10Z","timestamp":1755908410000},"source":"Crossref","is-referenced-by-count":0,"title":["\u03b1-catenin phosphorylation is actomyosin-sensitive and required for epithelial barrier functions through Afadin"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7830-4659","authenticated-orcid":false,"given":"Jeanne M.","family":"Quinn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0822-6668","authenticated-orcid":false,"given":"Phuong M.","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3909-8861","authenticated-orcid":false,"given":"Anthea","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0856-2670","authenticated-orcid":false,"given":"Annette S.","family":"Flozak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9778-9177","authenticated-orcid":false,"given":"S. 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