{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:50:51Z","timestamp":1792727451245,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["452622672"],"award-info":[{"award-number":["452622672"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["52622720"],"award-info":[{"award-number":["52622720"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["514478744"],"award-info":[{"award-number":["514478744"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["514477451"],"award-info":[{"award-number":["514477451"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Platelet function at vascular injury sites is tightly regulated through the actin cytoskeleton. The Wiskott\u2013Aldrich syndrome protein-family verprolin-homologous protein (WAVE)-regulatory complex (WRC) activates lamellipodia formation via ARP2\/3, initiated by GTP-bound RAC1 interacting with the WRC subunit CYFIP1. The protein FAM49b (Family of Unknown Function 49b), also known as CYRI-B (CYFIP-Related RAC Interactor B), has been found to interact with activated RAC1, leading to the negative regulation of the WRC in mammalian cells. To investigate the role of FAM49b in platelet function, we studied platelet-specific Fam49b\u2212\/\u2212-, Cyfip1\u2212\/\u2212-, and Cyfip1\/Fam49b\u2212\/\u2212-mice. Platelet counts and activation of Fam49b\u2212\/\u2212 mice were comparable to those of control mice. On fully fibrinogen-coated surfaces, Fam49b\u2212\/\u2212-platelets spread faster with an increased mean projected cell area than control platelets, whereas Cyfip1\/Fam49b\u2212\/\u2212-platelets did not form lamellipodia, phenocopying the Cyfip1\u2212\/\u2212-platelets. However, Fam49b\u2212\/\u2212-platelets often assumed a polarized shape and were more prone to migrate on fibrinogen-coated surfaces. On 2D structured micropatterns, however, Fam49b\u2212\/\u2212-platelets displayed reduced spreading, whereas spreading of Cyfip1\u2212\/\u2212- and Cyfip1\/Fam49b\u2212\/\u2212-platelets was enhanced. In summary, FAM49b contributes to the regulation of morphology and migration of spread platelets, but to exert its inhibitory effect on actin polymerization, the functional WAVE complex must be present.<\/jats:p>","DOI":"10.3390\/cells13040299","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T05:36:43Z","timestamp":1707197803000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential Role of the RAC1-Binding Proteins FAM49b (CYRI-B) and CYFIP1 in Platelets"],"prefix":"10.3390","volume":"13","author":[{"given":"Dmitri","family":"Sisario","sequence":"first","affiliation":[{"name":"Institute of Experimental Biomedicine\u2013Chair I, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Spindler","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine\u2013Chair I, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina J.","family":"Ermer","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine\u2013Chair I, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Gr\u00fctz","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine\u2013Chair I, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Nicolai","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, University Hospital Ludwig, Maximilian University, 81377 Munich, Germany"},{"name":"German Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gaertner","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, University Hospital Ludwig, Maximilian University, 81377 Munich, Germany"},{"name":"German Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7592-9856","authenticated-orcid":false,"given":"Laura M.","family":"Machesky","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, Sanger Building, 80 Tennis Court Road, Cambridge CB2 1GA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2381-116X","authenticated-orcid":false,"given":"Markus","family":"Bender","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine\u2013Chair I, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1161\/01.RES.0000267878.97021.ab","article-title":"Adhesion mechanisms in platelet function","volume":"100","author":"Ruggeri","year":"2007","journal-title":"Circ. 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