{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T10:31:57Z","timestamp":1758191517684,"version":"3.44.0"},"reference-count":57,"publisher":"Portland Press Ltd.","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9,17]]},"abstract":"<jats:p>Talin-1 is a central integrin adapter protein connecting cytoplasmic domains of integrins to the cytoskeleton. These talin-1-mediated mechanical linkages are crucial for cellular functions such as cell movement and connections with other cells. Here, we report a patient carrying a missense variant, L353F, in the talin-1 head which is associated with a complex set of symptoms, including skin lesions, blood cell abnormalities, and congenital cataracts. We conducted structural and cellular characterization of this variant. Recombinant talin-1 F2F3 fragment with the corresponding mutation showed a decrease in thermal stability and decreased solubility. Reconstitution of talin-deficient cells with L353F talin-1 revealed decreased cell migration velocity, defects in wound healing capacity, and changes in recruitment of the focal adhesion complex protein paxillin. We also observed decreased levels of activated integrin in cells expressing the talin-1 variant, while integrin-binding affinity was preserved as determined biochemically. These observations suggest that changes in integrin adhesion complex dynamics reflect cellular processes and the multifaceted patient phenotype.<\/jats:p>","DOI":"10.1042\/bcj20253128","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T14:33:35Z","timestamp":1758119615000},"page":"1337-1352","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>De novo<\/i> talin-1 variant L353F connects multifaceted clinical symptoms to alterations in talin-1 function"],"prefix":"10.1042","volume":"482","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0827-0800","authenticated-orcid":false,"given":"Muktesh","family":"Athale","sequence":"first","affiliation":[{"name":"1Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7165-6363","authenticated-orcid":false,"given":"Neil","family":"Ball","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry, Cell & Systems Biology, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, U.K"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7026-6507","authenticated-orcid":false,"given":"Latifeh","family":"Azizi","sequence":"additional","affiliation":[{"name":"1Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-6058","authenticated-orcid":false,"given":"Irene","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"3Clinical and Molecular Genetics Area, Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Codina","sequence":"additional","affiliation":[{"name":"3Clinical and Molecular Genetics Area, Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Martin-Nalda","sequence":"additional","affiliation":[{"name":"4Pediatric Infectious Diseases and Immunodeficiencies Unit, Children's Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2522-9907","authenticated-orcid":false,"given":"Vasyl V.","family":"Mykuliak","sequence":"additional","affiliation":[{"name":"1Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1265-862X","authenticated-orcid":false,"given":"Rolle","family":"Rahikainen","sequence":"additional","affiliation":[{"name":"1Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3438-2807","authenticated-orcid":false,"given":"Benjamin T.","family":"Goult","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry, Cell & Systems Biology, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, U.K"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5969-4807","authenticated-orcid":false,"given":"Paula","family":"Turkki","sequence":"additional","affiliation":[{"name":"1Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland"},{"name":"5Fimlab Laboratories, Tampere, 33520, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9357-1480","authenticated-orcid":false,"given":"Vesa P.","family":"Hyt\u00f6nen","sequence":"additional","affiliation":[{"name":"1Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland"},{"name":"5Fimlab Laboratories, Tampere, 33520, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"2025091710332864600_BCJ-2025-3128C1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41556-018-0234-9","article-title":"Integrin activation by talin, kindlin and mechanical forces","volume":"21","author":"Sun","year":"2019","journal-title":"Nat. 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