{"issue":"10","doi":"10.1016/j.cub.2021.02.043","acknowledgement":"We are grateful to Silvia Prettin, Ina Schleicher, and Petra Hagendorff for expert technical assistance; David Dettbarn for animal keeping and breeding; and Lothar Gröbe and Maria Höxter for cell sorting. We also thank Werner Tegge for peptides and Giorgio Scita for antibodies. This work was supported, in part, by the Deutsche Forschungsgemeinschaft (DFG), Priority Programm SPP1150 (to T.E.B.S., K.R., and M. Sixt), and by DFG grant GRK2223/1 (to K.R.). T.E.B.S. acknowledges support by the Helmholtz Society through HGF impulse fund W2/W3-066 and M. Schnoor by the Mexican Council for Science and Technology (CONACyT, 284292 ), Fund SEP-Cinvestav ( 108 ), and the Royal Society, UK (Newton Advanced Fellowship, NAF/R1/180017 ).","page":"2051-2064.e8","date_updated":"2023-08-17T07:01:14Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.03.24.005835"}],"publication":"Current Biology","_id":"10834","volume":31,"year":"2021","publisher":"Elsevier","day":"24","language":[{"iso":"eng"}],"oa":1,"publication_status":"published","external_id":{"isi":["000654652200002"],"pmid":["33711252"]},"isi":1,"author":[{"first_name":"Stephanie","full_name":"Stahnke, Stephanie","last_name":"Stahnke"},{"full_name":"Döring, Hermann","last_name":"Döring","first_name":"Hermann"},{"last_name":"Kusch","full_name":"Kusch, Charly","first_name":"Charly"},{"last_name":"de Gorter","full_name":"de Gorter, David J.J.","first_name":"David J.J."},{"full_name":"Dütting, Sebastian","last_name":"Dütting","first_name":"Sebastian"},{"full_name":"Guledani, Aleks","last_name":"Guledani","first_name":"Aleks"},{"first_name":"Irina","full_name":"Pleines, Irina","last_name":"Pleines"},{"first_name":"Michael","last_name":"Schnoor","full_name":"Schnoor, Michael"},{"first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","last_name":"Sixt"},{"first_name":"Robert","last_name":"Geffers","full_name":"Geffers, Robert"},{"first_name":"Manfred","full_name":"Rohde, Manfred","last_name":"Rohde"},{"full_name":"Müsken, Mathias","last_name":"Müsken","first_name":"Mathias"},{"last_name":"Kage","full_name":"Kage, Frieda","first_name":"Frieda"},{"last_name":"Steffen","full_name":"Steffen, Anika","first_name":"Anika"},{"first_name":"Jan","full_name":"Faix, Jan","last_name":"Faix"},{"first_name":"Bernhard","last_name":"Nieswandt","full_name":"Nieswandt, Bernhard"},{"first_name":"Klemens","full_name":"Rottner, Klemens","last_name":"Rottner"},{"first_name":"Theresia E.B.","last_name":"Stradal","full_name":"Stradal, Theresia E.B."}],"citation":{"ista":"Stahnke S, Döring H, Kusch C, de Gorter DJJ, Dütting S, Guledani A, Pleines I, Schnoor M, Sixt MK, Geffers R, Rohde M, Müsken M, Kage F, Steffen A, Faix J, Nieswandt B, Rottner K, Stradal TEB. 2021. Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion. Current Biology. 31(10), 2051–2064.e8.","short":"S. Stahnke, H. Döring, C. Kusch, D.J.J. de Gorter, S. Dütting, A. Guledani, I. Pleines, M. Schnoor, M.K. Sixt, R. Geffers, M. Rohde, M. Müsken, F. Kage, A. Steffen, J. Faix, B. Nieswandt, K. Rottner, T.E.B. Stradal, Current Biology 31 (2021) 2051–2064.e8.","ama":"Stahnke S, Döring H, Kusch C, et al. Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion. <i>Current Biology</i>. 2021;31(10):2051-2064.e8. doi:<a href=\"https://doi.org/10.1016/j.cub.2021.02.043\">10.1016/j.cub.2021.02.043</a>","chicago":"Stahnke, Stephanie, Hermann Döring, Charly Kusch, David J.J. de Gorter, Sebastian Dütting, Aleks Guledani, Irina Pleines, et al. “Loss of Hem1 Disrupts Macrophage Function and Impacts Migration, Phagocytosis, and Integrin-Mediated Adhesion.” <i>Current Biology</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.cub.2021.02.043\">https://doi.org/10.1016/j.cub.2021.02.043</a>.","ieee":"S. Stahnke <i>et al.</i>, “Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion,” <i>Current Biology</i>, vol. 31, no. 10. Elsevier, p. 2051–2064.e8, 2021.","mla":"Stahnke, Stephanie, et al. “Loss of Hem1 Disrupts Macrophage Function and Impacts Migration, Phagocytosis, and Integrin-Mediated Adhesion.” <i>Current Biology</i>, vol. 31, no. 10, Elsevier, 2021, p. 2051–2064.e8, doi:<a href=\"https://doi.org/10.1016/j.cub.2021.02.043\">10.1016/j.cub.2021.02.043</a>.","apa":"Stahnke, S., Döring, H., Kusch, C., de Gorter, D. J. J., Dütting, S., Guledani, A., … Stradal, T. E. B. (2021). Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion. <i>Current Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cub.2021.02.043\">https://doi.org/10.1016/j.cub.2021.02.043</a>"},"intvolume":"        31","department":[{"_id":"MiSi"}],"quality_controlled":"1","scopus_import":"1","pmid":1,"abstract":[{"text":"Hematopoietic-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.","lang":"eng"}],"type":"journal_article","publication_identifier":{"issn":["0960-9822"]},"month":"05","oa_version":"Preprint","date_created":"2022-03-08T07:51:04Z","date_published":"2021-05-24T00:00:00Z","keyword":["General Agricultural and Biological Sciences","General Biochemistry","Genetics and Molecular Biology"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","article_type":"original","status":"public","title":"Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion"}