[{"date_published":"2021-01-05T00:00:00Z","doi":"10.1073/pnas.2010054118","date_created":"2021-01-03T23:01:23Z","day":"05","publication":"PNAS","isi":1,"year":"2021","publisher":"National Academy of Sciences","quality_controlled":"1","oa":1,"acknowledgement":"We thank Urban Bezeljak, Natalia Baranova, Mar Lopez-Pelegrin, Catarina Alcarva, and Victoria Faas for sharing reagents and helpful discussions. We thank Veronika Szentirmai for help with protein purifications. We thank Carrie Bernecky, Sascha Martens, and the M.L. lab for comments on the manuscript. We thank the bioimaging facility, the life science facility, and Armel Nicolas from the mass spec facility at the Institute of Science and Technology (IST) Austria for technical support. C.D. acknowledges funding from the IST fellowship program; this work was supported by Human Frontier Science Program Young Investigator Grant\r\nRGY0083/2016. ","title":"In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1","author":[{"last_name":"Düllberg","full_name":"Düllberg, Christian F","orcid":"0000-0001-6335-9748","first_name":"Christian F","id":"459064DC-F248-11E8-B48F-1D18A9856A87"},{"id":"3018E8C2-F248-11E8-B48F-1D18A9856A87","first_name":"Albert","full_name":"Auer, Albert","orcid":"0000-0002-3580-2906","last_name":"Auer"},{"last_name":"Canigova","orcid":"0000-0002-8518-5926","full_name":"Canigova, Nikola","id":"3795523E-F248-11E8-B48F-1D18A9856A87","first_name":"Nikola"},{"last_name":"Loibl","full_name":"Loibl, Katrin","orcid":"0000-0002-2429-7668","first_name":"Katrin","id":"3760F32C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Loose, Martin","orcid":"0000-0001-7309-9724","last_name":"Loose","id":"462D4284-F248-11E8-B48F-1D18A9856A87","first_name":"Martin"}],"article_processing_charge":"No","external_id":{"pmid":["33443153"],"isi":["000607270100018"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Düllberg, Christian F, Albert Auer, Nikola Canigova, Katrin Loibl, and Martin Loose. “In Vitro Reconstitution Reveals Phosphoinositides as Cargo-Release Factors and Activators of the ARF6 GAP ADAP1.” PNAS. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.2010054118.","ista":"Düllberg CF, Auer A, Canigova N, Loibl K, Loose M. 2021. In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1. PNAS. 118(1), e2010054118.","mla":"Düllberg, Christian F., et al. “In Vitro Reconstitution Reveals Phosphoinositides as Cargo-Release Factors and Activators of the ARF6 GAP ADAP1.” PNAS, vol. 118, no. 1, e2010054118, National Academy of Sciences, 2021, doi:10.1073/pnas.2010054118.","ieee":"C. F. Düllberg, A. Auer, N. Canigova, K. Loibl, and M. Loose, “In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1,” PNAS, vol. 118, no. 1. National Academy of Sciences, 2021.","short":"C.F. Düllberg, A. Auer, N. Canigova, K. Loibl, M. Loose, PNAS 118 (2021).","ama":"Düllberg CF, Auer A, Canigova N, Loibl K, Loose M. In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1. PNAS. 2021;118(1). doi:10.1073/pnas.2010054118","apa":"Düllberg, C. F., Auer, A., Canigova, N., Loibl, K., & Loose, M. (2021). In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.2010054118"},"project":[{"name":"Reconstitution of cell polarity and axis determination in a cell-free system","grant_number":"RGY0083/2016","_id":"2599F062-B435-11E9-9278-68D0E5697425"}],"article_number":"e2010054118","issue":"1","volume":118,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["10916490"],"issn":["00278424"]},"publication_status":"published","month":"01","intvolume":" 118","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.2010054118"}],"pmid":1,"oa_version":"Published Version","abstract":[{"text":"The differentiation of cells depends on a precise control of their internal organization, which is the result of a complex dynamic interplay between the cytoskeleton, molecular motors, signaling molecules, and membranes. For example, in the developing neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP] with dual pleckstrin homology [PH] domains 1) has been suggested to control dendrite branching by regulating the small GTPase ARF6. Together with the motor protein KIF13B, ADAP1 is also thought to mediate delivery of the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to the axon tip, thus contributing to PIP3 polarity. However, what defines the function of ADAP1 and how its different roles are coordinated are still not clear. Here, we studied ADAP1’s functions using in vitro reconstitutions. We found that KIF13B transports ADAP1 along microtubules, but that PIP3 as well as PI(3,4)P2 act as stop signals for this transport instead of being transported. We also demonstrate that these phosphoinositides activate ADAP1’s enzymatic activity to catalyze GTP hydrolysis by ARF6. Together, our results support a model for the cellular function of ADAP1, where KIF13B transports ADAP1 until it encounters high PIP3/PI(3,4)P2 concentrations in the plasma membrane. Here, ADAP1 disassociates from the motor to inactivate ARF6, promoting dendrite branching.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"department":[{"_id":"MaLo"},{"_id":"MiSi"}],"date_updated":"2023-08-04T11:20:46Z","status":"public","type":"journal_article","article_type":"original","_id":"8988"},{"publication":"Frontiers in Immunology","day":"25","year":"2021","has_accepted_license":"1","isi":1,"date_created":"2021-03-21T23:01:20Z","doi":"10.3389/fimmu.2021.630002","date_published":"2021-02-25T00:00:00Z","acknowledgement":"This work was supported by Sigrid Juselius fellowship (KV), University of Helsinki 3-year research grant (KV), Academy of Finland Research fellow funding (315710, to KV), the European Research Council (ERC CoG 724373 to MS), and by the Austrian Science foundation (FWF) (Y564-B12 START award to MS).\r\nTaija Mäkinen is acknowledged for providing Prox1CreERT2 transgenic mice and Yu Yamaguchi for providing the conditional Ext1 mouse strain.","oa":1,"quality_controlled":"1","publisher":"Frontiers","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Vaahtomeri, Kari, Christine Moussion, Robert Hauschild, and Michael K Sixt. “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.” Frontiers in Immunology. Frontiers, 2021. https://doi.org/10.3389/fimmu.2021.630002.","ista":"Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. 2021. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. 12, 630002.","mla":"Vaahtomeri, Kari, et al. “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.” Frontiers in Immunology, vol. 12, 630002, Frontiers, 2021, doi:10.3389/fimmu.2021.630002.","apa":"Vaahtomeri, K., Moussion, C., Hauschild, R., & Sixt, M. K. (2021). Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. Frontiers. https://doi.org/10.3389/fimmu.2021.630002","ama":"Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. 2021;12. doi:10.3389/fimmu.2021.630002","ieee":"K. Vaahtomeri, C. Moussion, R. Hauschild, and M. K. Sixt, “Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium,” Frontiers in Immunology, vol. 12. Frontiers, 2021.","short":"K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology 12 (2021)."},"title":"Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium","article_processing_charge":"No","external_id":{"isi":["000627134400001"],"pmid":["33717158"]},"author":[{"first_name":"Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","last_name":"Vaahtomeri","orcid":"0000-0001-7829-3518","full_name":"Vaahtomeri, Kari"},{"last_name":"Moussion","full_name":"Moussion, Christine","first_name":"Christine","id":"3356F664-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","last_name":"Hauschild"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K"}],"article_number":"630002","project":[{"grant_number":"724373","name":"Cellular navigation along spatial gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"FWF","_id":"25A8E5EA-B435-11E9-9278-68D0E5697425","grant_number":"Y 564-B12","name":"Cytoskeletal force generation and force transduction of migrating leukocytes"}],"language":[{"iso":"eng"}],"file":[{"success":1,"checksum":"663f5a48375e42afa4bfef58d42ec186","file_id":"9277","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2021_FrontiersImmumo_Vaahtomeri.pdf","date_created":"2021-03-22T12:08:26Z","file_size":3740146,"date_updated":"2021-03-22T12:08:26Z","creator":"dernst"}],"publication_status":"published","publication_identifier":{"eissn":["1664-3224"]},"license":"https://creativecommons.org/licenses/by/4.0/","ec_funded":1,"volume":12,"oa_version":"Published Version","pmid":1,"abstract":[{"lang":"eng","text":"Gradients of chemokines and growth factors guide migrating cells and morphogenetic processes. Migration of antigen-presenting dendritic cells from the interstitium into the lymphatic system is dependent on chemokine CCL21, which is secreted by endothelial cells of the lymphatic capillary, binds heparan sulfates and forms gradients decaying into the interstitium. Despite the importance of CCL21 gradients, and chemokine gradients in general, the mechanisms of gradient formation are unclear. Studies on fibroblast growth factors have shown that limited diffusion is crucial for gradient formation. Here, we used the mouse dermis as a model tissue to address the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels at the lymphatic capillaries and did neither affect interstitial CCL21 gradient shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan sulfates at the level of the lymphatic endothelium are dispensable for the formation of a functional CCL21 gradient."}],"intvolume":" 12","month":"02","scopus_import":"1","ddc":["570"],"date_updated":"2023-08-07T14:18:26Z","department":[{"_id":"MiSi"},{"_id":"Bio"}],"file_date_updated":"2021-03-22T12:08:26Z","_id":"9259","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original"},{"article_type":"original","type":"journal_article","status":"public","_id":"9294","department":[{"_id":"MiSi"}],"date_updated":"2023-08-07T14:26:47Z","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.devcel.2021.03.002"}],"month":"03","intvolume":" 56","abstract":[{"lang":"eng","text":"In this issue of Developmental Cell, Doyle and colleagues identify periodic anterior contraction as a characteristic feature of fibroblasts and mesenchymal cancer cells embedded in 3D collagen gels. This contractile mechanism generates a matrix prestrain required for crawling in fibrous 3D environments."}],"pmid":1,"oa_version":"Published Version","issue":"6","volume":56,"publication_identifier":{"eissn":["18781551"],"issn":["15345807"]},"publication_status":"published","language":[{"iso":"eng"}],"author":[{"last_name":"Gärtner","full_name":"Gärtner, Florian R","orcid":"0000-0001-6120-3723","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","first_name":"Florian R"},{"last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000631681200004"],"pmid":["33756118"]},"article_processing_charge":"No","title":"Engaging the front wheels to drive through fibrous terrain","citation":{"apa":"Gärtner, F. R., & Sixt, M. K. (2021). Engaging the front wheels to drive through fibrous terrain. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2021.03.002","ama":"Gärtner FR, Sixt MK. Engaging the front wheels to drive through fibrous terrain. Developmental Cell. 2021;56(6):723-725. doi:10.1016/j.devcel.2021.03.002","short":"F.R. Gärtner, M.K. Sixt, Developmental Cell 56 (2021) 723–725.","ieee":"F. R. Gärtner and M. K. Sixt, “Engaging the front wheels to drive through fibrous terrain,” Developmental Cell, vol. 56, no. 6. Elsevier, pp. 723–725, 2021.","mla":"Gärtner, Florian R., and Michael K. Sixt. “Engaging the Front Wheels to Drive through Fibrous Terrain.” Developmental Cell, vol. 56, no. 6, Elsevier, 2021, pp. 723–25, doi:10.1016/j.devcel.2021.03.002.","ista":"Gärtner FR, Sixt MK. 2021. Engaging the front wheels to drive through fibrous terrain. Developmental Cell. 56(6), 723–725.","chicago":"Gärtner, Florian R, and Michael K Sixt. “Engaging the Front Wheels to Drive through Fibrous Terrain.” Developmental Cell. Elsevier, 2021. https://doi.org/10.1016/j.devcel.2021.03.002."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","quality_controlled":"1","publisher":"Elsevier","oa":1,"page":"723-725","doi":"10.1016/j.devcel.2021.03.002","date_published":"2021-03-22T00:00:00Z","date_created":"2021-03-28T22:01:41Z","isi":1,"year":"2021","day":"22","publication":"Developmental Cell"},{"title":"Sequential and switchable patterning for studying cellular processes under spatiotemporal control","external_id":{"pmid":["34283577"],"isi":["000683741400026"]},"article_processing_charge":"Yes (in subscription journal)","author":[{"full_name":"Zisis, Themistoklis","last_name":"Zisis","first_name":"Themistoklis"},{"last_name":"Schwarz","full_name":"Schwarz, Jan","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Miriam","full_name":"Balles, Miriam","last_name":"Balles"},{"last_name":"Kretschmer","full_name":"Kretschmer, Maibritt","first_name":"Maibritt"},{"full_name":"Nemethova, Maria","last_name":"Nemethova","first_name":"Maria","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P","last_name":"Chait","first_name":"Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert"},{"full_name":"Lange, Janina","last_name":"Lange","first_name":"Janina"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K"},{"first_name":"Stefan","full_name":"Zahler, Stefan","last_name":"Zahler"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ama":"Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 2021;13(30):35545–35560. doi:10.1021/acsami.1c09850","apa":"Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R. P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. American Chemical Society. https://doi.org/10.1021/acsami.1c09850","ieee":"T. Zisis et al., “Sequential and switchable patterning for studying cellular processes under spatiotemporal control,” ACS Applied Materials and Interfaces, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.","short":"T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait, R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials and Interfaces 13 (2021) 35545–35560.","mla":"Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and Interfaces, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560, doi:10.1021/acsami.1c09850.","ista":"Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 13(30), 35545–35560.","chicago":"Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and Interfaces. American Chemical Society, 2021. https://doi.org/10.1021/acsami.1c09850."},"project":[{"grant_number":"724373","name":"Cellular navigation along spatial gradients","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"date_created":"2021-08-08T22:01:28Z","date_published":"2021-08-04T00:00:00Z","doi":"10.1021/acsami.1c09850","page":"35545–35560","publication":"ACS Applied Materials and Interfaces","day":"04","year":"2021","isi":1,"has_accepted_license":"1","oa":1,"publisher":"American Chemical Society","quality_controlled":"1","acknowledgement":"We would like to thank Charlott Leu for the production of our chromium wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim Rädler for his valuable scientific guidance.","file_date_updated":"2021-08-09T09:44:03Z","department":[{"_id":"MiSi"},{"_id":"GaTk"},{"_id":"Bio"},{"_id":"CaGu"}],"ddc":["620","570"],"date_updated":"2023-08-10T14:22:48Z","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"article_type":"original","type":"journal_article","_id":"9822","ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","issue":"30","volume":13,"language":[{"iso":"eng"}],"file":[{"date_updated":"2021-08-09T09:44:03Z","file_size":7123293,"creator":"asandaue","date_created":"2021-08-09T09:44:03Z","file_name":"2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"b043a91d9f9200e467b970b692687ed3","file_id":"9833","success":1}],"publication_status":"published","publication_identifier":{"eissn":["19448252"],"issn":["19448244"]},"intvolume":" 13","month":"08","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"text":"Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science.","lang":"eng"}]},{"date_updated":"2023-08-17T07:01:14Z","department":[{"_id":"MiSi"}],"_id":"10834","article_type":"original","type":"journal_article","keyword":["General Agricultural and Biological Sciences","General Biochemistry","Genetics and Molecular Biology"],"status":"public","publication_status":"published","publication_identifier":{"issn":["0960-9822"]},"language":[{"iso":"eng"}],"issue":"10","volume":31,"abstract":[{"lang":"eng","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."}],"pmid":1,"oa_version":"Preprint","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.03.24.005835"}],"scopus_import":"1","intvolume":" 31","month":"05","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.","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.” Current Biology. Elsevier, 2021. https://doi.org/10.1016/j.cub.2021.02.043.","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. Current Biology. Elsevier. https://doi.org/10.1016/j.cub.2021.02.043","ama":"Stahnke S, Döring H, Kusch C, et al. Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion. Current Biology. 2021;31(10):2051-2064.e8. doi:10.1016/j.cub.2021.02.043","ieee":"S. Stahnke et al., “Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion,” Current Biology, vol. 31, no. 10. Elsevier, p. 2051–2064.e8, 2021.","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.","mla":"Stahnke, Stephanie, et al. “Loss of Hem1 Disrupts Macrophage Function and Impacts Migration, Phagocytosis, and Integrin-Mediated Adhesion.” Current Biology, vol. 31, no. 10, Elsevier, 2021, p. 2051–2064.e8, doi:10.1016/j.cub.2021.02.043."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"pmid":["33711252"],"isi":["000654652200002"]},"article_processing_charge":"No","author":[{"last_name":"Stahnke","full_name":"Stahnke, Stephanie","first_name":"Stephanie"},{"first_name":"Hermann","full_name":"Döring, Hermann","last_name":"Döring"},{"last_name":"Kusch","full_name":"Kusch, Charly","first_name":"Charly"},{"first_name":"David J.J.","last_name":"de Gorter","full_name":"de Gorter, David J.J."},{"first_name":"Sebastian","last_name":"Dütting","full_name":"Dütting, Sebastian"},{"first_name":"Aleks","full_name":"Guledani, Aleks","last_name":"Guledani"},{"first_name":"Irina","last_name":"Pleines","full_name":"Pleines, Irina"},{"last_name":"Schnoor","full_name":"Schnoor, Michael","first_name":"Michael"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"},{"first_name":"Robert","last_name":"Geffers","full_name":"Geffers, Robert"},{"last_name":"Rohde","full_name":"Rohde, Manfred","first_name":"Manfred"},{"full_name":"Müsken, Mathias","last_name":"Müsken","first_name":"Mathias"},{"first_name":"Frieda","last_name":"Kage","full_name":"Kage, Frieda"},{"last_name":"Steffen","full_name":"Steffen, Anika","first_name":"Anika"},{"first_name":"Jan","full_name":"Faix, Jan","last_name":"Faix"},{"first_name":"Bernhard","full_name":"Nieswandt, Bernhard","last_name":"Nieswandt"},{"full_name":"Rottner, Klemens","last_name":"Rottner","first_name":"Klemens"},{"last_name":"Stradal","full_name":"Stradal, Theresia E.B.","first_name":"Theresia E.B."}],"title":"Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion","year":"2021","isi":1,"publication":"Current Biology","day":"24","page":"2051-2064.e8","date_created":"2022-03-08T07:51:04Z","doi":"10.1016/j.cub.2021.02.043","date_published":"2021-05-24T00:00:00Z","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 ).","oa":1,"quality_controlled":"1","publisher":"Elsevier"},{"abstract":[{"text":"Dendritic cells (DCs) are crucial for the priming of naive T cells and the initiation of adaptive immunity. Priming is initiated at a heterologous cell–cell contact, the immunological synapse (IS). While it is established that F-actin dynamics regulates signaling at the T cell side of the contact, little is known about the cytoskeletal contribution on the DC side. Here, we show that the DC actin cytoskeleton is decisive for the formation of a multifocal synaptic structure, which correlates with T cell priming efficiency. DC actin at the IS appears in transient foci that are dynamized by the WAVE regulatory complex (WRC). The absence of the WRC in DCs leads to stabilized contacts with T cells, caused by an increase in ICAM1-integrin–mediated cell–cell adhesion. This results in lower numbers of activated and proliferating T cells, demonstrating an important role for DC actin in the regulation of immune synapse functionality.","lang":"eng"}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","intvolume":" 220","month":"04","publication_status":"published","publication_identifier":{"eissn":["1540-8140"],"issn":["0021-9525"]},"language":[{"iso":"eng"}],"file":[{"checksum":"843ebc153847c8626e13c9c5ce71d533","file_id":"11367","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2022-05-12T14:16:21Z","file_name":"2021_JournCellBiology_Leithner.pdf","creator":"dernst","date_updated":"2022-05-12T14:16:21Z","file_size":5102328}],"license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","volume":220,"issue":"4","_id":"9094","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"type":"journal_article","article_type":"original","status":"public","date_updated":"2023-09-05T13:57:53Z","ddc":["570"],"department":[{"_id":"MiSi"}],"file_date_updated":"2022-05-12T14:16:21Z","oa":1,"quality_controlled":"1","publisher":"Rockefeller University Press","year":"2021","has_accepted_license":"1","isi":1,"publication":"Journal of Cell Biology","day":"05","date_created":"2021-02-05T10:08:04Z","date_published":"2021-04-05T00:00:00Z","doi":"10.1083/jcb.202006081","article_number":"e202006081","citation":{"chicago":"Leithner, Alexander F, LM Altenburger, R Hauschild, Frank P Assen, K Rottner, Stradal TEB, A Diz-Muñoz, JV Stein, and Michael K Sixt. “Dendritic Cell Actin Dynamics Control Contact Duration and Priming Efficiency at the Immunological Synapse.” Journal of Cell Biology. Rockefeller University Press, 2021. https://doi.org/10.1083/jcb.202006081.","ista":"Leithner AF, Altenburger L, Hauschild R, Assen FP, Rottner K, TEB S, Diz-Muñoz A, Stein J, Sixt MK. 2021. Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. Journal of Cell Biology. 220(4), e202006081.","mla":"Leithner, Alexander F., et al. “Dendritic Cell Actin Dynamics Control Contact Duration and Priming Efficiency at the Immunological Synapse.” Journal of Cell Biology, vol. 220, no. 4, e202006081, Rockefeller University Press, 2021, doi:10.1083/jcb.202006081.","ama":"Leithner AF, Altenburger L, Hauschild R, et al. Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. Journal of Cell Biology. 2021;220(4). doi:10.1083/jcb.202006081","apa":"Leithner, A. F., Altenburger, L., Hauschild, R., Assen, F. P., Rottner, K., TEB, S., … Sixt, M. K. (2021). Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.202006081","short":"A.F. Leithner, L. Altenburger, R. Hauschild, F.P. Assen, K. Rottner, S. TEB, A. Diz-Muñoz, J. Stein, M.K. Sixt, Journal of Cell Biology 220 (2021).","ieee":"A. F. Leithner et al., “Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse,” Journal of Cell Biology, vol. 220, no. 4. Rockefeller University Press, 2021."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"isi":["000626365700001"],"pmid":["33533935"]},"article_processing_charge":"No","author":[{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F"},{"full_name":"Altenburger, LM","last_name":"Altenburger","first_name":"LM"},{"last_name":"Hauschild","full_name":"Hauschild, R","first_name":"R"},{"first_name":"Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","last_name":"Assen","full_name":"Assen, Frank P","orcid":"0000-0003-3470-6119"},{"first_name":"K","full_name":"Rottner, K","last_name":"Rottner"},{"first_name":"Stradal","full_name":"TEB, Stradal","last_name":"TEB"},{"first_name":"A","last_name":"Diz-Muñoz","full_name":"Diz-Muñoz, A"},{"last_name":"Stein","full_name":"Stein, JV","first_name":"JV"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt"}],"title":"Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse"},{"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"9430","checksum":"337e0f7959c35ec959984cacdcb472ba","success":1,"creator":"kschuh","date_updated":"2021-05-28T12:39:43Z","file_size":9358599,"date_created":"2021-05-28T12:39:43Z","file_name":"2021_NatureCommunications_Morandell.pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2041-1723"]},"publication_status":"published","volume":12,"issue":"1","related_material":{"record":[{"relation":"earlier_version","id":"7800","status":"public"},{"status":"public","id":"12401","relation":"dissertation_contains"}],"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}]},"ec_funded":1,"oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"}],"abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.","lang":"eng"}],"month":"05","intvolume":" 12","ddc":["572"],"date_updated":"2024-03-27T23:30:23Z","file_date_updated":"2021-05-28T12:39:43Z","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"_id":"9429","status":"public","keyword":["General Biochemistry","Genetics and Molecular Biology"],"type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"24","publication":"Nature Communications","has_accepted_license":"1","isi":1,"year":"2021","doi":"10.1038/s41467-021-23123-x","date_published":"2021-05-24T00:00:00Z","date_created":"2021-05-28T11:49:46Z","acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","publisher":"Springer Nature","quality_controlled":"1","oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x."},"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","author":[{"full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schwarz, Lena A","last_name":"Schwarz","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","last_name":"Basilico"},{"full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X","last_name":"Tasciyan","first_name":"Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","last_name":"Dimchev","full_name":"Dimchev, Georgi A","orcid":"0000-0001-8370-6161"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"},{"last_name":"Dotter","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","last_name":"Knaus","full_name":"Knaus, Lisa"},{"last_name":"Dobler","full_name":"Dobler, Zoe","first_name":"Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F"},{"last_name":"Cacci","full_name":"Cacci, Emanuele","first_name":"Emanuele"},{"first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur"},{"last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"article_processing_charge":"No","external_id":{"isi":["000658769900010"]},"article_number":"3058","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"}]},{"day":"18","year":"2021","has_accepted_license":"1","date_created":"2021-11-18T15:05:06Z","date_published":"2021-11-18T00:00:00Z","doi":"10.15479/at:ista:10307","page":"73","oa":1,"publisher":"Institute of Science and Technology Austria","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Tomasek, Kathrin. Pathogenic Escherichia Coli Hijack the Host Immune Response. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307.","ieee":"K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021.","short":"K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response, Institute of Science and Technology Austria, 2021.","apa":"Tomasek, K. (2021). Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10307","ama":"Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021. doi:10.15479/at:ista:10307","chicago":"Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10307.","ista":"Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria."},"title":"Pathogenic Escherichia coli hijack the host immune response","article_processing_charge":"No","author":[{"orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin","last_name":"Tomasek","first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"}],"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"10308","checksum":"b39c9e0ef18d0484d537a67551effd02","embargo":"2022-11-18","date_updated":"2022-12-20T23:30:05Z","file_size":13266088,"creator":"ktomasek","date_created":"2021-11-18T15:07:31Z","file_name":"ThesisTomasekKathrin.pdf"},{"checksum":"c0c440ee9e5ef1102a518a4f9f023e7c","file_id":"10309","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","access_level":"closed","relation":"source_file","date_created":"2021-11-18T15:07:46Z","file_name":"ThesisTomasekKathrin.docx","date_updated":"2022-12-20T23:30:05Z","file_size":7539509,"creator":"ktomasek"}],"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"id":"10316","status":"public","relation":"part_of_dissertation"}]},"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response."}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"month":"11","alternative_title":["ISTA Thesis"],"ddc":["570"],"date_updated":"2023-09-07T13:34:38Z","supervisor":[{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-4561-241X","last_name":"Sixt"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"}],"file_date_updated":"2022-12-20T23:30:05Z","department":[{"_id":"MiSi"},{"_id":"CaGu"},{"_id":"GradSch"}],"_id":"10307","status":"public","type":"dissertation"},{"_id":"10316","project":[{"grant_number":"724373","name":"Cellular navigation along spatial gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"P29911","name":"Mechanical adaptation of lamellipodial actin","_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"status":"public","type":"preprint","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, 10.1101/2021.10.18.464770.","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2021.10.18.464770.","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv. doi:10.1101/2021.10.18.464770","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., & Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2021.10.18.464770"},"date_updated":"2024-03-27T23:30:35Z","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","department":[{"_id":"CaGu"},{"_id":"MiSi"}],"article_processing_charge":"No","author":[{"full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","last_name":"Tomasek","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin"},{"first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X","last_name":"Leithner"},{"full_name":"Glatzová, Ivana","last_name":"Glatzová","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","first_name":"Ivana"},{"first_name":"Michael S.","last_name":"Lukesch","full_name":"Lukesch, Michael S."},{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","last_name":"Sixt"}],"acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","oa_version":"Preprint","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"month":"10","oa":1,"main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1"}],"publisher":"Cold Spring Harbor Laboratory","language":[{"iso":"eng"}],"publication":"bioRxiv","day":"18","publication_status":"submitted","year":"2021","date_created":"2021-11-19T12:24:16Z","ec_funded":1,"date_published":"2021-10-18T00:00:00Z","doi":"10.1101/2021.10.18.464770","related_material":{"record":[{"status":"public","id":"11843","relation":"later_version"},{"relation":"dissertation_contains","id":"10307","status":"public"}]}},{"_id":"7234","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","date_updated":"2023-08-17T14:21:12Z","ddc":["570"],"department":[{"_id":"MiSi"}],"file_date_updated":"2020-11-19T11:22:33Z","abstract":[{"lang":"eng","text":"T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin‐related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F‐actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3‐knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon‐like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three‐dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3‐dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities."}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","month":"02","intvolume":" 98","publication_identifier":{"issn":["08189641"],"eissn":["14401711"]},"publication_status":"published","file":[{"file_name":"2020_ImmunologyCellBio_Obeidy.pdf","date_created":"2020-11-19T11:22:33Z","creator":"dernst","file_size":8569945,"date_updated":"2020-11-19T11:22:33Z","success":1,"file_id":"8775","checksum":"c389477b4b52172ef76afff8a06c6775","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"volume":98,"issue":"2","citation":{"mla":"Obeidy, Peyman, et al. “Partial Loss of Actin Nucleator Actin-Related Protein 2/3 Activity Triggers Blebbing in Primary T Lymphocytes.” Immunology and Cell Biology, vol. 98, no. 2, Wiley, 2020, pp. 93–113, doi:10.1111/imcb.12304.","short":"P. Obeidy, L.A. Ju, S.H. Oehlers, N.S. Zulkhernain, Q. Lee, J.L. Galeano Niño, R.Y.Q. Kwan, S. Tikoo, L.L. Cavanagh, P. Mrass, A.J.L. Cook, S.P. Jackson, M. Biro, B. Roediger, M.K. Sixt, W. Weninger, Immunology and Cell Biology 98 (2020) 93–113.","ieee":"P. Obeidy et al., “Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes,” Immunology and Cell Biology, vol. 98, no. 2. Wiley, pp. 93–113, 2020.","apa":"Obeidy, P., Ju, L. A., Oehlers, S. H., Zulkhernain, N. S., Lee, Q., Galeano Niño, J. L., … Weninger, W. (2020). Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology. Wiley. https://doi.org/10.1111/imcb.12304","ama":"Obeidy P, Ju LA, Oehlers SH, et al. Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology. 2020;98(2):93-113. doi:10.1111/imcb.12304","chicago":"Obeidy, Peyman, Lining A. Ju, Stefan H. Oehlers, Nursafwana S. Zulkhernain, Quintin Lee, Jorge L. Galeano Niño, Rain Y.Q. Kwan, et al. “Partial Loss of Actin Nucleator Actin-Related Protein 2/3 Activity Triggers Blebbing in Primary T Lymphocytes.” Immunology and Cell Biology. Wiley, 2020. https://doi.org/10.1111/imcb.12304.","ista":"Obeidy P, Ju LA, Oehlers SH, Zulkhernain NS, Lee Q, Galeano Niño JL, Kwan RYQ, Tikoo S, Cavanagh LL, Mrass P, Cook AJL, Jackson SP, Biro M, Roediger B, Sixt MK, Weninger W. 2020. Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology. 98(2), 93–113."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Peyman","last_name":"Obeidy","full_name":"Obeidy, Peyman"},{"last_name":"Ju","full_name":"Ju, Lining A.","first_name":"Lining A."},{"first_name":"Stefan H.","last_name":"Oehlers","full_name":"Oehlers, Stefan H."},{"full_name":"Zulkhernain, Nursafwana S.","last_name":"Zulkhernain","first_name":"Nursafwana S."},{"full_name":"Lee, Quintin","last_name":"Lee","first_name":"Quintin"},{"first_name":"Jorge L.","full_name":"Galeano Niño, Jorge L.","last_name":"Galeano Niño"},{"full_name":"Kwan, Rain Y.Q.","last_name":"Kwan","first_name":"Rain Y.Q."},{"first_name":"Shweta","last_name":"Tikoo","full_name":"Tikoo, Shweta"},{"full_name":"Cavanagh, Lois L.","last_name":"Cavanagh","first_name":"Lois L."},{"last_name":"Mrass","full_name":"Mrass, Paulus","first_name":"Paulus"},{"first_name":"Adam J.L.","last_name":"Cook","full_name":"Cook, Adam J.L."},{"first_name":"Shaun P.","last_name":"Jackson","full_name":"Jackson, Shaun P."},{"full_name":"Biro, Maté","last_name":"Biro","first_name":"Maté"},{"last_name":"Roediger","full_name":"Roediger, Ben","first_name":"Ben"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"},{"first_name":"Wolfgang","last_name":"Weninger","full_name":"Weninger, Wolfgang"}],"article_processing_charge":"No","external_id":{"pmid":["31698518"],"isi":["000503885600001"]},"title":"Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes","publisher":"Wiley","quality_controlled":"1","oa":1,"isi":1,"has_accepted_license":"1","year":"2020","day":"01","publication":"Immunology and Cell Biology","page":"93-113","date_published":"2020-02-01T00:00:00Z","doi":"10.1111/imcb.12304","date_created":"2020-01-05T23:00:48Z"}]