--- _id: '12119' abstract: - lang: eng text: Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events. acknowledgement: "We thank Coung Kieu and Dominik van den Heuvel for excellent technical assistance. This work was supported by the German Research Foundation (PE2704/2-1, PE2704/3-1 to T.P., SFB 1123-project B06 to S.M., SFB1525 project A07 to D.S, TRR 332 project A7 to C.S., PO 2247/2-1 to A.P., SFB1116-project B11 to A.P. and B12 to M.K.), LMU Munich’s Institutional\r\nStrategy LMUexcellent within the framework of the German Excellence Initiative (No. 806 32 006 to T.P.), and by the German Centre for Cardiovascular Research (DZHK) to T.P. (Postdoc Start-up grant No. 100378833). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 833440 to S.M.). F.G. received funding from the European Union’s\r\nHorizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement no. 747687. A.H. was funded by RTI2018-095497-B-I00 from Ministerio de Ciencia e Innovacio´ n (MICINN), HR17_00527 from Fundacion La Caixa, and Transatlantic Network of Excellence (TNE-18CVD04) from the Leducq Foundation. The CNIC is supported by the MICINN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). A.P. was supported by the Forschungskommission of the Medical Faculty of the Heinrich-Heine-Universität Düsseldorf (No. 18-2019 to A.P.). C.G. was supported by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro,’ by the German Federal\r\nMinistry of Education and Research to the German Center for Diabetes Research (DZD), and by the Bavarian State Ministry of Health and Care through the research project DigiMed Bayern." article_processing_charge: No article_type: original author: - first_name: Tobias full_name: Petzold, Tobias last_name: Petzold - first_name: Zhe full_name: Zhang, Zhe last_name: Zhang - first_name: Iván full_name: Ballesteros, Iván last_name: Ballesteros - first_name: Inas full_name: Saleh, Inas last_name: Saleh - first_name: Amin full_name: Polzin, Amin last_name: Polzin - first_name: Manuela full_name: Thienel, Manuela last_name: Thienel - first_name: Lulu full_name: Liu, Lulu last_name: Liu - first_name: Qurrat full_name: Ul Ain, Qurrat last_name: Ul Ain - first_name: Vincent full_name: Ehreiser, Vincent last_name: Ehreiser - first_name: Christian full_name: Weber, Christian last_name: Weber - first_name: Badr full_name: Kilani, Badr last_name: Kilani - first_name: Pontus full_name: Mertsch, Pontus last_name: Mertsch - first_name: Jeremias full_name: Götschke, Jeremias last_name: Götschke - first_name: Sophie full_name: Cremer, Sophie last_name: Cremer - first_name: Wenwen full_name: Fu, Wenwen last_name: Fu - first_name: Michael full_name: Lorenz, Michael last_name: Lorenz - first_name: Hellen full_name: Ishikawa-Ankerhold, Hellen last_name: Ishikawa-Ankerhold - first_name: Elisabeth full_name: Raatz, Elisabeth last_name: Raatz - first_name: Shaza full_name: El-Nemr, Shaza last_name: El-Nemr - first_name: Agnes full_name: Görlach, Agnes last_name: Görlach - first_name: Esther full_name: Marhuenda, Esther last_name: Marhuenda - first_name: Konstantin full_name: Stark, Konstantin last_name: Stark - first_name: Joachim full_name: Pircher, Joachim last_name: Pircher - first_name: David full_name: Stegner, David last_name: Stegner - first_name: Christian full_name: Gieger, Christian last_name: Gieger - first_name: Marc full_name: Schmidt-Supprian, Marc last_name: Schmidt-Supprian - first_name: Florian R full_name: Gärtner, Florian R id: 397A88EE-F248-11E8-B48F-1D18A9856A87 last_name: Gärtner orcid: 0000-0001-6120-3723 - first_name: Isaac full_name: Almendros, Isaac last_name: Almendros - first_name: Malte full_name: Kelm, Malte last_name: Kelm - first_name: Christian full_name: Schulz, Christian last_name: Schulz - first_name: Andrés full_name: Hidalgo, Andrés last_name: Hidalgo - first_name: Steffen full_name: Massberg, Steffen last_name: Massberg citation: ama: Petzold T, Zhang Z, Ballesteros I, et al. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 2022;55(12):2285-2299.e7. doi:10.1016/j.immuni.2022.10.001 apa: Petzold, T., Zhang, Z., Ballesteros, I., Saleh, I., Polzin, A., Thienel, M., … Massberg, S. (2022). Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2022.10.001 chicago: Petzold, Tobias, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin, Manuela Thienel, Lulu Liu, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity. Elsevier, 2022. https://doi.org/10.1016/j.immuni.2022.10.001. ieee: T. Petzold et al., “Neutrophil ‘plucking’ on megakaryocytes drives platelet production and boosts cardiovascular disease,” Immunity, vol. 55, no. 12. Elsevier, p. 2285–2299.e7, 2022. ista: Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gärtner FR, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. 2022. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 55(12), 2285–2299.e7. mla: Petzold, Tobias, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity, vol. 55, no. 12, Elsevier, 2022, p. 2285–2299.e7, doi:10.1016/j.immuni.2022.10.001. short: T. Petzold, Z. Zhang, I. Ballesteros, I. Saleh, A. Polzin, M. Thienel, L. Liu, Q. Ul Ain, V. Ehreiser, C. Weber, B. Kilani, P. Mertsch, J. Götschke, S. Cremer, W. Fu, M. Lorenz, H. Ishikawa-Ankerhold, E. Raatz, S. El-Nemr, A. Görlach, E. Marhuenda, K. Stark, J. Pircher, D. Stegner, C. Gieger, M. Schmidt-Supprian, F.R. Gärtner, I. Almendros, M. Kelm, C. Schulz, A. Hidalgo, S. Massberg, Immunity 55 (2022) 2285–2299.e7. date_created: 2023-01-12T11:56:54Z date_published: 2022-12-13T00:00:00Z date_updated: 2023-08-03T14:21:51Z day: '13' ddc: - '570' department: - _id: MiSi doi: 10.1016/j.immuni.2022.10.001 ec_funded: 1 external_id: isi: - '000922019600003' pmid: - '36272416' file: - access_level: open_access checksum: 073267a9c0ad9f85a650053bc7b23777 content_type: application/pdf creator: dernst date_created: 2023-01-23T10:18:48Z date_updated: 2023-01-23T10:18:48Z file_id: '12341' file_name: 2022_Immunity_Petzold.pdf file_size: 5299475 relation: main_file success: 1 file_date_updated: 2023-01-23T10:18:48Z has_accepted_license: '1' intvolume: ' 55' isi: 1 issue: '12' keyword: - Infectious Diseases - Immunology - Immunology and Allergy language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 2285-2299.e7 pmid: 1 project: - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells publication: Immunity publication_identifier: issn: - 1074-7613 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 55 year: '2022' ... --- _id: '12133' abstract: - lang: eng text: Social distancing is an effective way to prevent the spread of disease in societies, whereas infection elimination is a key element of organismal immunity. Here, we discuss how the study of social insects such as ants — which form a superorganism of unconditionally cooperative individuals and thus represent a level of organization that is intermediate between a classical society of individuals and an organism of cells — can help to determine common principles of disease defence across levels of organization. article_processing_charge: No article_type: letter_note author: - first_name: Sylvia full_name: Cremer, Sylvia id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87 last_name: Cremer orcid: 0000-0002-2193-3868 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Cremer S, Sixt MK. Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. 2022;22(12):713-714. doi:10.1038/s41577-022-00797-y apa: Cremer, S., & Sixt, M. K. (2022). Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. Springer Nature. https://doi.org/10.1038/s41577-022-00797-y chicago: Cremer, Sylvia, and Michael K Sixt. “Principles of Disease Defence in Organisms, Superorganisms and Societies.” Nature Reviews Immunology. Springer Nature, 2022. https://doi.org/10.1038/s41577-022-00797-y. ieee: S. Cremer and M. K. Sixt, “Principles of disease defence in organisms, superorganisms and societies,” Nature Reviews Immunology, vol. 22, no. 12. Springer Nature, pp. 713–714, 2022. ista: Cremer S, Sixt MK. 2022. Principles of disease defence in organisms, superorganisms and societies. Nature Reviews Immunology. 22(12), 713–714. mla: Cremer, Sylvia, and Michael K. Sixt. “Principles of Disease Defence in Organisms, Superorganisms and Societies.” Nature Reviews Immunology, vol. 22, no. 12, Springer Nature, 2022, pp. 713–14, doi:10.1038/s41577-022-00797-y. short: S. Cremer, M.K. Sixt, Nature Reviews Immunology 22 (2022) 713–714. date_created: 2023-01-12T12:03:14Z date_published: 2022-12-01T00:00:00Z date_updated: 2023-08-04T08:53:32Z day: '01' department: - _id: SyCr - _id: MiSi doi: 10.1038/s41577-022-00797-y external_id: isi: - '000871836300001' pmid: - '36284178' intvolume: ' 22' isi: 1 issue: '12' keyword: - Energy Engineering and Power Technology - Fuel Technology language: - iso: eng month: '12' oa_version: None page: 713-714 pmid: 1 publication: Nature Reviews Immunology publication_identifier: eissn: - 1474-1741 issn: - 1474-1733 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Principles of disease defence in organisms, superorganisms and societies type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 22 year: '2022' ... --- _id: '12272' abstract: - lang: eng text: Reading, interpreting and crawling along gradients of chemotactic cues is one of the most complex questions in cell biology. In this issue, Georgantzoglou et al. (2022. J. Cell. Biol.https://doi.org/10.1083/jcb.202103207) use in vivo models to map the temporal sequence of how neutrophils respond to an acutely arising gradient of chemoattractant. article_number: e202206127 article_processing_charge: No article_type: original author: - first_name: Julian A full_name: Stopp, Julian A id: 489E3F00-F248-11E8-B48F-1D18A9856A87 last_name: Stopp - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: 'Stopp JA, Sixt MK. Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. 2022;221(8). doi:10.1083/jcb.202206127' apa: 'Stopp, J. A., & Sixt, M. K. (2022). Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.202206127' chicago: 'Stopp, Julian A, and Michael K Sixt. “Plan Your Trip before You Leave: The Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology. Rockefeller University Press, 2022. https://doi.org/10.1083/jcb.202206127.' ieee: 'J. A. Stopp and M. K. Sixt, “Plan your trip before you leave: The neutrophils’ search-and-run journey,” Journal of Cell Biology, vol. 221, no. 8. Rockefeller University Press, 2022.' ista: 'Stopp JA, Sixt MK. 2022. Plan your trip before you leave: The neutrophils’ search-and-run journey. Journal of Cell Biology. 221(8), e202206127.' mla: 'Stopp, Julian A., and Michael K. Sixt. “Plan Your Trip before You Leave: The Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology, vol. 221, no. 8, e202206127, Rockefeller University Press, 2022, doi:10.1083/jcb.202206127.' short: J.A. Stopp, M.K. Sixt, Journal of Cell Biology 221 (2022). date_created: 2023-01-16T10:01:08Z date_published: 2022-07-20T00:00:00Z date_updated: 2023-12-21T14:30:01Z day: '20' ddc: - '570' department: - _id: MiSi doi: 10.1083/jcb.202206127 external_id: isi: - '000874717200001' pmid: - '35856919' file: - access_level: open_access checksum: 6b1620743669679b48b9389bb40f5a11 content_type: application/pdf creator: dernst date_created: 2023-01-30T10:39:34Z date_updated: 2023-01-30T10:39:34Z file_id: '12451' file_name: 2022_JourCellBiology_Stopp.pdf file_size: 969969 relation: main_file success: 1 file_date_updated: 2023-01-30T10:39:34Z has_accepted_license: '1' intvolume: ' 221' isi: 1 issue: '8' keyword: - Cell Biology language: - iso: eng license: https://creativecommons.org/licenses/by-nc-sa/4.0/ month: '07' oa: 1 oa_version: Published Version pmid: 1 publication: Journal of Cell Biology publication_identifier: eissn: - 1540-8140 issn: - 0021-9525 publication_status: published publisher: Rockefeller University Press quality_controlled: '1' related_material: record: - id: '14697' relation: dissertation_contains status: public scopus_import: '1' status: public title: 'Plan your trip before you leave: The neutrophils’ search-and-run journey' tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 221 year: '2022' ... --- _id: '10703' abstract: - lang: eng text: 'When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.' acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: EM-Fac acknowledgement: We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687. article_processing_charge: No article_type: original author: - first_name: Florian full_name: Gaertner, Florian last_name: Gaertner - first_name: Patricia full_name: Reis-Rodrigues, Patricia last_name: Reis-Rodrigues - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Juan full_name: Aguilera, Juan last_name: Aguilera - first_name: Michael full_name: Riedl, Michael id: 3BE60946-F248-11E8-B48F-1D18A9856A87 last_name: Riedl orcid: 0000-0003-4844-6311 - first_name: Alexander F full_name: Leithner, Alexander F id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87 last_name: Leithner orcid: 0000-0002-1073-744X - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Vanessa full_name: Zheden, Vanessa id: 39C5A68A-F248-11E8-B48F-1D18A9856A87 last_name: Zheden orcid: 0000-0002-9438-4783 - first_name: Walter full_name: Kaufmann, Walter id: 3F99E422-F248-11E8-B48F-1D18A9856A87 last_name: Kaufmann orcid: 0000-0001-9735-5315 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 2022;57(1):47-62.e9. doi:10.1016/j.devcel.2021.11.024 apa: Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl, M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. Cell Press ; Elsevier. https://doi.org/10.1016/j.devcel.2021.11.024 chicago: Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell. Cell Press ; Elsevier, 2022. https://doi.org/10.1016/j.devcel.2021.11.024. ieee: F. Gaertner et al., “WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues,” Developmental Cell, vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022. ista: Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 57(1), 47–62.e9. mla: Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” Developmental Cell, vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:10.1016/j.devcel.2021.11.024. short: F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl, A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild, M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9. date_created: 2022-01-30T23:01:33Z date_published: 2022-01-10T00:00:00Z date_updated: 2024-03-27T23:30:23Z day: '10' ddc: - '570' department: - _id: MiSi - _id: EM-Fac - _id: NanoFab - _id: BjHo doi: 10.1016/j.devcel.2021.11.024 ec_funded: 1 external_id: isi: - '000768933800005' pmid: - '34919802' intvolume: ' 57' isi: 1 issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://www.sciencedirect.com/science/article/pii/S1534580721009497 month: '01' oa: 1 oa_version: Published Version page: 47-62.e9 pmid: 1 project: - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: Developmental Cell publication_identifier: eissn: - 1878-1551 issn: - 1534-5807 publication_status: published publisher: Cell Press ; Elsevier quality_controlled: '1' related_material: record: - id: '12726' relation: dissertation_contains status: public - id: '14530' relation: dissertation_contains status: public - id: '12401' relation: dissertation_contains status: public scopus_import: '1' status: public title: WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 57 year: '2022' ... --- _id: '12401' abstract: - lang: eng text: "Detachment of the cancer cells from the bulk of the tumor is the first step of metastasis, which\r\nis the primary cause of cancer related deaths. It is unclear, which factors contribute to this step.\r\nRecent studies indicate a crucial role of the tumor microenvironment in malignant\r\ntransformation and metastasis. Studying cancer cell invasion and detachments quantitatively in\r\nthe context of its physiological microenvironment is technically challenging. Especially, precise\r\ncontrol of microenvironmental properties in vivo is currently not possible. Here, I studied the\r\nrole of microenvironment geometry in the invasion and detachment of cancer cells from the\r\nbulk with a simplistic and reductionist approach. In this approach, I engineered microfluidic\r\ndevices to mimic a pseudo 3D extracellular matrix environment, where I was able to\r\nquantitatively tune the geometrical configuration of the microenvironment and follow tumor\r\ncells with fluorescence live imaging. To aid quantitative analysis I developed a widely applicable\r\nsoftware application to automatically analyze and visualize particle tracking data.\r\nQuantitative analysis of tumor cell invasion in isotropic and anisotropic microenvironments\r\nshowed that heterogeneity in the microenvironment promotes faster invasion and more\r\nfrequent detachment of cells. These observations correlated with overall higher speed of cells at\r\nthe edge of the bulk of the cells. In heterogeneous microenvironments cells preferentially\r\npassed through larger pores, thus invading areas of least resistance and generating finger-like\r\ninvasive structures. The detachments occurred mostly at the tips of these structures.\r\nTo investigate the potential mechanism, we established a two dimensional model to simulate\r\nactive Brownian particles representing the cell nuclei dynamics. These simulations backed our in\r\nvitro observations without the need of precise fitting the simulation parameters. Our model\r\nsuggests the importance of the pore heterogeneity in the direction perpendicular to the\r\norientation of bias field (lateral heterogeneity), which causes the interface roughening." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X citation: ama: Tasciyan S. Role of microenvironment heterogeneity in cancer cell invasion. 2022. doi:10.15479/at:ista:12401 apa: Tasciyan, S. (2022). Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12401 chicago: Tasciyan, Saren. “Role of Microenvironment Heterogeneity in Cancer Cell Invasion.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12401. ieee: S. Tasciyan, “Role of microenvironment heterogeneity in cancer cell invasion,” Institute of Science and Technology Austria, 2022. ista: Tasciyan S. 2022. Role of microenvironment heterogeneity in cancer cell invasion. Institute of Science and Technology Austria. mla: Tasciyan, Saren. Role of Microenvironment Heterogeneity in Cancer Cell Invasion. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12401. short: S. Tasciyan, Role of Microenvironment Heterogeneity in Cancer Cell Invasion, Institute of Science and Technology Austria, 2022. date_created: 2023-01-26T11:55:16Z date_published: 2022-12-22T00:00:00Z date_updated: 2023-12-21T23:30:04Z day: '22' ddc: - '610' degree_awarded: PhD department: - _id: GradSch - _id: MiSi doi: 10.15479/at:ista:12401 file: - access_level: open_access checksum: cc4a2b4a7e3c4ee8ef7f2dbf909b12bd content_type: application/pdf creator: cchlebak date_created: 2023-01-26T11:58:14Z date_updated: 2023-12-21T23:30:03Z embargo: 2023-12-20 file_id: '12402' file_name: PhD-Thesis_Saren Tasciyan_formatted_aftercrash_fixed_600dpi_95pc_final_PDFA3b.pdf file_size: 42059787 relation: main_file - access_level: closed checksum: f1b4ca98b8ab0cb043b1830971e9bd9c content_type: application/x-zip-compressed creator: cchlebak date_created: 2023-01-26T12:00:10Z date_updated: 2023-12-21T23:30:03Z embargo_to: open_access file_id: '12403' file_name: Source Files - Saren Tasciyan - PhD Thesis.zip file_size: 261256696 relation: source_file file_date_updated: 2023-12-21T23:30:03Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '105' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '679' relation: part_of_dissertation status: public - id: '10703' relation: part_of_dissertation status: public - id: '9429' relation: part_of_dissertation status: public - id: '7885' relation: part_of_dissertation status: public status: public supervisor: - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 title: Role of microenvironment heterogeneity in cancer cell invasion type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2022' ... --- _id: '8988' abstract: - lang: eng 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. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: EM-Fac 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. " article_number: e2010054118 article_processing_charge: No article_type: original author: - first_name: Christian F full_name: Düllberg, Christian F id: 459064DC-F248-11E8-B48F-1D18A9856A87 last_name: Düllberg orcid: 0000-0001-6335-9748 - first_name: Albert full_name: Auer, Albert id: 3018E8C2-F248-11E8-B48F-1D18A9856A87 last_name: Auer orcid: 0000-0002-3580-2906 - first_name: Nikola full_name: Canigova, Nikola id: 3795523E-F248-11E8-B48F-1D18A9856A87 last_name: Canigova orcid: 0000-0002-8518-5926 - first_name: Katrin full_name: Loibl, Katrin id: 3760F32C-F248-11E8-B48F-1D18A9856A87 last_name: Loibl orcid: 0000-0002-2429-7668 - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 citation: 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 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. 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. 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. short: C.F. Düllberg, A. Auer, N. Canigova, K. Loibl, M. Loose, PNAS 118 (2021). date_created: 2021-01-03T23:01:23Z date_published: 2021-01-05T00:00:00Z date_updated: 2023-08-04T11:20:46Z day: '05' department: - _id: MaLo - _id: MiSi doi: 10.1073/pnas.2010054118 external_id: isi: - '000607270100018' pmid: - '33443153' intvolume: ' 118' isi: 1 issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1073/pnas.2010054118 month: '01' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 2599F062-B435-11E9-9278-68D0E5697425 grant_number: RGY0083/2016 name: Reconstitution of cell polarity and axis determination in a cell-free system publication: PNAS publication_identifier: eissn: - '10916490' issn: - '00278424' publication_status: published publisher: National Academy of Sciences quality_controlled: '1' scopus_import: '1' status: public title: In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1 type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 118 year: '2021' ... --- _id: '9259' 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. 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." article_number: '630002' article_processing_charge: No article_type: original author: - first_name: Kari full_name: Vaahtomeri, Kari id: 368EE576-F248-11E8-B48F-1D18A9856A87 last_name: Vaahtomeri orcid: 0000-0001-7829-3518 - first_name: Christine full_name: Moussion, Christine id: 3356F664-F248-11E8-B48F-1D18A9856A87 last_name: Moussion - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: 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 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 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. 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. 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. short: K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology 12 (2021). date_created: 2021-03-21T23:01:20Z date_published: 2021-02-25T00:00:00Z date_updated: 2023-08-07T14:18:26Z day: '25' ddc: - '570' department: - _id: MiSi - _id: Bio doi: 10.3389/fimmu.2021.630002 ec_funded: 1 external_id: isi: - '000627134400001' pmid: - '33717158' file: - access_level: open_access checksum: 663f5a48375e42afa4bfef58d42ec186 content_type: application/pdf creator: dernst date_created: 2021-03-22T12:08:26Z date_updated: 2021-03-22T12:08:26Z file_id: '9277' file_name: 2021_FrontiersImmumo_Vaahtomeri.pdf file_size: 3740146 relation: main_file success: 1 file_date_updated: 2021-03-22T12:08:26Z has_accepted_license: '1' intvolume: ' 12' isi: 1 language: - iso: eng month: '02' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 25A8E5EA-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Y 564-B12 name: Cytoskeletal force generation and force transduction of migrating leukocytes publication: Frontiers in Immunology publication_identifier: eissn: - 1664-3224 publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ... --- _id: '9294' 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. article_processing_charge: No article_type: original author: - first_name: Florian R full_name: Gärtner, Florian R id: 397A88EE-F248-11E8-B48F-1D18A9856A87 last_name: Gärtner orcid: 0000-0001-6120-3723 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: 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 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 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. 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. ista: Gärtner FR, Sixt MK. 2021. Engaging the front wheels to drive through fibrous terrain. Developmental Cell. 56(6), 723–725. 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. short: F.R. Gärtner, M.K. Sixt, Developmental Cell 56 (2021) 723–725. date_created: 2021-03-28T22:01:41Z date_published: 2021-03-22T00:00:00Z date_updated: 2023-08-07T14:26:47Z day: '22' department: - _id: MiSi doi: 10.1016/j.devcel.2021.03.002 external_id: isi: - '000631681200004' pmid: - '33756118' intvolume: ' 56' isi: 1 issue: '6' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.devcel.2021.03.002 month: '03' oa: 1 oa_version: Published Version page: 723-725 pmid: 1 publication: Developmental Cell publication_identifier: eissn: - '18781551' issn: - '15345807' publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Engaging the front wheels to drive through fibrous terrain type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 56 year: '2021' ... --- _id: '9822' abstract: - lang: eng 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. 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. article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Themistoklis full_name: Zisis, Themistoklis last_name: Zisis - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Miriam full_name: Balles, Miriam last_name: Balles - first_name: Maibritt full_name: Kretschmer, Maibritt last_name: Kretschmer - first_name: Maria full_name: Nemethova, Maria id: 34E27F1C-F248-11E8-B48F-1D18A9856A87 last_name: Nemethova - first_name: Remy P full_name: Chait, Remy P id: 3464AE84-F248-11E8-B48F-1D18A9856A87 last_name: Chait orcid: 0000-0003-0876-3187 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Janina full_name: Lange, Janina last_name: Lange - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-4561-241X - first_name: Stefan full_name: Zahler, Stefan last_name: Zahler 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 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. 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. 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. 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. 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. date_created: 2021-08-08T22:01:28Z date_published: 2021-08-04T00:00:00Z date_updated: 2023-08-10T14:22:48Z day: '04' ddc: - '620' - '570' department: - _id: MiSi - _id: GaTk - _id: Bio - _id: CaGu doi: 10.1021/acsami.1c09850 ec_funded: 1 external_id: isi: - '000683741400026' pmid: - '34283577' file: - access_level: open_access checksum: b043a91d9f9200e467b970b692687ed3 content_type: application/pdf creator: asandaue date_created: 2021-08-09T09:44:03Z date_updated: 2021-08-09T09:44:03Z file_id: '9833' file_name: 2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf file_size: 7123293 relation: main_file success: 1 file_date_updated: 2021-08-09T09:44:03Z has_accepted_license: '1' intvolume: ' 13' isi: 1 issue: '30' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: 35545–35560 pmid: 1 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: ACS Applied Materials and Interfaces publication_identifier: eissn: - '19448252' issn: - '19448244' publication_status: published publisher: American Chemical Society quality_controlled: '1' scopus_import: '1' status: public title: Sequential and switchable patterning for studying cellular processes under spatiotemporal control tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 13 year: '2021' ... --- _id: '10834' 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. 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 ). article_processing_charge: No article_type: original author: - first_name: Stephanie full_name: Stahnke, Stephanie last_name: Stahnke - first_name: Hermann full_name: Döring, Hermann last_name: Döring - first_name: Charly full_name: Kusch, Charly last_name: Kusch - first_name: David J.J. full_name: de Gorter, David J.J. last_name: de Gorter - first_name: Sebastian full_name: Dütting, Sebastian last_name: Dütting - first_name: Aleks full_name: Guledani, Aleks last_name: Guledani - first_name: Irina full_name: Pleines, Irina last_name: Pleines - first_name: Michael full_name: Schnoor, Michael last_name: Schnoor - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 - first_name: Robert full_name: Geffers, Robert last_name: Geffers - first_name: Manfred full_name: Rohde, Manfred last_name: Rohde - first_name: Mathias full_name: Müsken, Mathias last_name: Müsken - first_name: Frieda full_name: Kage, Frieda last_name: Kage - first_name: Anika full_name: Steffen, Anika last_name: Steffen - first_name: Jan full_name: Faix, Jan last_name: Faix - first_name: Bernhard full_name: Nieswandt, Bernhard last_name: Nieswandt - first_name: Klemens full_name: Rottner, Klemens last_name: Rottner - first_name: Theresia E.B. full_name: Stradal, Theresia E.B. last_name: Stradal citation: 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 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 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. 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. 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. 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. 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. date_created: 2022-03-08T07:51:04Z date_published: 2021-05-24T00:00:00Z date_updated: 2023-08-17T07:01:14Z day: '24' department: - _id: MiSi doi: 10.1016/j.cub.2021.02.043 external_id: isi: - '000654652200002' pmid: - '33711252' intvolume: ' 31' isi: 1 issue: '10' keyword: - General Agricultural and Biological Sciences - General Biochemistry - Genetics and Molecular Biology language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.03.24.005835 month: '05' oa: 1 oa_version: Preprint page: 2051-2064.e8 pmid: 1 publication: Current Biology publication_identifier: issn: - 0960-9822 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Loss of Hem1 disrupts macrophage function and impacts migration, phagocytosis, and integrin-mediated adhesion type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 31 year: '2021' ...