{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:21:18Z","timestamp":1792790478202,"version":"4.5.0"},"reference-count":52,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T00:00:00Z","timestamp":1484524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T00:00:00Z","timestamp":1484524800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T00:00:00Z","timestamp":1484524800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["National grant"],"award-info":[{"award-number":["National grant"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Conselleria Valenciana d'Educaci\u00f3 i Ci\u00e8ncia","award":["Graduate student fellowship"],"award-info":[{"award-number":["Graduate student fellowship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of \u03b15\u03b21, \u03b1IIb\u03b23 and \u03b1v-class integrins to an RGD-motif. An additional linkage for \u03b15 and \u03b1IIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (Fn1syn\/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of \u03b23 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensable for the initial contact of \u03b15\u03b21 with the RGD, but essential to re-enforce the binding of \u03b15\u03b21\/\u03b1IIb\u03b23 to FN. Our findings demonstrate a critical role for the FN synergy site when external forces exceed a certain threshold or when \u03b1v\u03b23 integrin levels decrease below a critical level.<\/jats:p>","DOI":"10.7554\/elife.22264","type":"journal-article","created":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T08:03:03Z","timestamp":1484553783000},"source":"Crossref","is-referenced-by-count":94,"title":["The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9562-5430","authenticated-orcid":true,"given":"Maria","family":"Benito-Jard\u00f3n","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Universitat de Val\u00e8ncia, Burjassot, Spain"},{"name":"Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina, Universitat de Val\u00e8ncia, Burjassot, 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