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dc.contributor.authorStahnke, Stephanie
dc.contributor.authorDöring, Hermann
dc.contributor.authorKusch, Charly
dc.contributor.authorde Gorter, David J J
dc.contributor.authorDütting, Sebastian
dc.contributor.authorGuledani, Aleks
dc.contributor.authorPleines, Irina
dc.contributor.authorSchnoor, Michael
dc.contributor.authorSixt, Michael
dc.contributor.authorGeffers, Robert
dc.contributor.authorRohde, Manfred
dc.contributor.authorMüsken, Mathias
dc.contributor.authorKage, Frieda
dc.contributor.authorSteffen, Anika
dc.contributor.authorFaix, Jan
dc.contributor.authorNieswandt, Bernhard
dc.contributor.authorRottner, Klemens
dc.contributor.authorStradal, Theresia E B
dc.date.accessioned2021-07-22T09:05:42Z
dc.date.available2021-07-22T09:05:42Z
dc.date.issued2021-03-11
dc.identifier.citationCurr Biol. 2021 May 24;31(10):2051-2064.e8. doi: 10.1016/j.cub.2021.02.043. Epub 2021 Mar 11.en_US
dc.identifier.pmid33711252
dc.identifier.doi10.1016/j.cub.2021.02.043
dc.identifier.urihttp://hdl.handle.net/10033/622951
dc.description.abstractHematopoietic-specific protein 1 (Hem1) is an essential subunit of the WAVE regulatory complex (WRC) in immune cells. WRC is crucial for Arp2/3 complex activation and the protrusion of branched actin filament networks. Moreover, Hem1 loss of function in immune cells causes autoimmune diseases in humans. Here, we show that genetic removal of Hem1 in macrophages diminishes frequency and efficacy of phagocytosis as well as phagocytic cup formation in addition to defects in lamellipodial protrusion and migration. Moreover, Hem1-null macrophages displayed strong defects in cell adhesion despite unaltered podosome formation and concomitant extracellular matrix degradation. Specifically, dynamics of both adhesion and de-adhesion as well as concomitant phosphorylation of paxillin and focal adhesion kinase (FAK) were significantly compromised. Accordingly, disruption of WRC function in non-hematopoietic cells coincided with both defects in adhesion turnover and altered FAK and paxillin phosphorylation. Consistently, platelets exhibited reduced adhesion and diminished integrin αIIbβ3 activation upon WRC removal. Interestingly, adhesion phenotypes, but not lamellipodia formation, were partially rescued by small molecule activation of FAK. A full rescue of the phenotype, including lamellipodia formation, required not only the presence of WRCs but also their binding to and activation by Rac. Collectively, our results uncover that WRC impacts on integrin-dependent processes in a FAK-dependent manner, controlling formation and dismantling of adhesions, relevant for properly grabbing onto extracellular surfaces and particles during cell edge expansion, like in migration or phagocytosis.en_US
dc.language.isoenen_US
dc.publisherWiley-VCHen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectHem1en_US
dc.subjectWAVE regulatory complexen_US
dc.subjectWRCen_US
dc.subjectadhesionen_US
dc.subjectintegrinen_US
dc.subjectknockouten_US
dc.subjectmacrophageen_US
dc.subjectphagocytosisen_US
dc.subjectprotrusionen_US
dc.subjectrescueen_US
dc.titleLoss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion.en_US
dc.typeArticleen_US
dc.identifier.eissn1879-0445
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalCurrent biology : CBen_US
dc.source.volume31
dc.source.issue10
dc.source.beginpage2051
dc.source.endpage2064.e8
refterms.dateFOA2021-07-22T09:05:43Z
dc.source.journaltitleCurrent biology : CB
dc.source.countryEngland


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Attribution 4.0 International
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