--- _id: '1910' abstract: - lang: eng text: angerhans cells (LCs) are a unique subset of dendritic cells (DCs) that express epithelial adhesion molecules, allowing them to form contacts with epithelial cells and reside in epidermal/epithelial tissues. The dynamic regulation of epithelial adhesion plays a decisive role in the life cycle of LCs. It controls whether LCs remain immature and sessile within the epidermis or mature and egress to initiate immune responses. So far, the molecular machinery regulating epithelial adhesion molecules during LC maturation remains elusive. Here, we generated pure populations of immature human LCs in vitro to systematically probe for gene-expression changes during LC maturation. LCs down-regulate a set of epithelial genes including E-cadherin, while they upregulate the mesenchymal marker N-cadherin known to facilitate cell migration. In addition, N-cadherin is constitutively expressed by monocyte-derived DCs known to exhibit characteristics of both inflammatory-type and interstitial/dermal DCs. Moreover, the transcription factors ZEB1 and ZEB2 (ZEB is zinc-finger E-box-binding homeobox) are upregulated in migratory LCs. ZEB1 and ZEB2 have been shown to induce epithelial-to-mesenchymal transition (EMT) and invasive behavior in cancer cells undergoing metastasis. Our results provide the first hint that the molecular EMT machinery might facilitate LC mobilization. Moreover, our study suggests that N-cadherin plays a role during DC migration. acknowledgement: 'FWF. Grant Number: P22058-B20' author: - first_name: Sabine full_name: Konradi, Sabine last_name: Konradi - first_name: Nighat full_name: Yasmin, Nighat last_name: Yasmin - first_name: Denise full_name: Haslwanter, Denise last_name: Haslwanter - first_name: Michele full_name: Weber, Michele id: 3A3FC708-F248-11E8-B48F-1D18A9856A87 last_name: Weber - first_name: Bernd full_name: Gesslbauer, Bernd last_name: Gesslbauer - 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: Herbert full_name: Strobl, Herbert last_name: Strobl citation: ama: Konradi S, Yasmin N, Haslwanter D, et al. Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2. European Journal of Immunology. 2014;44(2):553-560. doi:10.1002/eji.201343681 apa: Konradi, S., Yasmin, N., Haslwanter, D., Weber, M., Gesslbauer, B., Sixt, M. K., & Strobl, H. (2014). Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2. European Journal of Immunology. Wiley-Blackwell. https://doi.org/10.1002/eji.201343681 chicago: Konradi, Sabine, Nighat Yasmin, Denise Haslwanter, Michele Weber, Bernd Gesslbauer, Michael K Sixt, and Herbert Strobl. “Langerhans Cell Maturation Is Accompanied by Induction of N-Cadherin and the Transcriptional Regulators of Epithelial-Mesenchymal Transition ZEB1/2.” European Journal of Immunology. Wiley-Blackwell, 2014. https://doi.org/10.1002/eji.201343681. ieee: S. Konradi et al., “Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2,” European Journal of Immunology, vol. 44, no. 2. Wiley-Blackwell, pp. 553–560, 2014. ista: Konradi S, Yasmin N, Haslwanter D, Weber M, Gesslbauer B, Sixt MK, Strobl H. 2014. Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2. European Journal of Immunology. 44(2), 553–560. mla: Konradi, Sabine, et al. “Langerhans Cell Maturation Is Accompanied by Induction of N-Cadherin and the Transcriptional Regulators of Epithelial-Mesenchymal Transition ZEB1/2.” European Journal of Immunology, vol. 44, no. 2, Wiley-Blackwell, 2014, pp. 553–60, doi:10.1002/eji.201343681. short: S. Konradi, N. Yasmin, D. Haslwanter, M. Weber, B. Gesslbauer, M.K. Sixt, H. Strobl, European Journal of Immunology 44 (2014) 553–560. date_created: 2018-12-11T11:54:40Z date_published: 2014-02-01T00:00:00Z date_updated: 2021-01-12T06:54:01Z day: '01' department: - _id: MiSi doi: 10.1002/eji.201343681 intvolume: ' 44' issue: '2' language: - iso: eng month: '02' oa_version: None page: 553 - 560 publication: European Journal of Immunology publication_status: published publisher: Wiley-Blackwell publist_id: '5185' scopus_import: 1 status: public title: Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2 type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 44 year: '2014' ... --- _id: '2839' abstract: - lang: eng text: Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues. acknowledgement: We thank M. Frank for technical assistance and S. Cremer, P. Schmalhorst, and E. Kiermaier for critical reading of the manuscript. This work was supported by a Humboldt Foundation postdoctoral fellowship (to M.W.), the German Research Foundation (Si1323 1,2 to M.S.), the Human Frontier Science Program (HFSP RGP0058/2011 to M.S.), the European Research Council (ERC StG 281556 to M.S.), and the Swiss National Science Foundation (31003A 127474 to D.F.L., 130488 to S.A.L.). article_processing_charge: No article_type: original author: - first_name: Michele full_name: Weber, Michele id: 3A3FC708-F248-11E8-B48F-1D18A9856A87 last_name: Weber - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Jan full_name: Schwarz, Jan id: 346C1EC6-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Christine full_name: Moussion, Christine id: 3356F664-F248-11E8-B48F-1D18A9856A87 last_name: Moussion - first_name: Ingrid full_name: De Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: De Vries - first_name: Daniel full_name: Legler, Daniel last_name: Legler - first_name: Sanjiv full_name: Luther, Sanjiv last_name: Luther - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X - 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: Weber M, Hauschild R, Schwarz J, et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. 2013;339(6117):328-332. doi:10.1126/science.1228456 apa: Weber, M., Hauschild, R., Schwarz, J., Moussion, C., de Vries, I., Legler, D., … Sixt, M. K. (2013). Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1228456 chicago: Weber, Michele, Robert Hauschild, Jan Schwarz, Christine Moussion, Ingrid de Vries, Daniel Legler, Sanjiv Luther, Mark Tobias Bollenbach, and Michael K Sixt. “Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients.” Science. American Association for the Advancement of Science, 2013. https://doi.org/10.1126/science.1228456. ieee: M. Weber et al., “Interstitial dendritic cell guidance by haptotactic chemokine gradients,” Science, vol. 339, no. 6117. American Association for the Advancement of Science, pp. 328–332, 2013. ista: Weber M, Hauschild R, Schwarz J, Moussion C, de Vries I, Legler D, Luther S, Bollenbach MT, Sixt MK. 2013. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science. 339(6117), 328–332. mla: Weber, Michele, et al. “Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients.” Science, vol. 339, no. 6117, American Association for the Advancement of Science, 2013, pp. 328–32, doi:10.1126/science.1228456. short: M. Weber, R. Hauschild, J. Schwarz, C. Moussion, I. de Vries, D. Legler, S. Luther, M.T. Bollenbach, M.K. Sixt, Science 339 (2013) 328–332. date_created: 2018-12-11T11:59:52Z date_published: 2013-01-18T00:00:00Z date_updated: 2022-06-10T10:21:40Z day: '18' department: - _id: MiSi - _id: Bio doi: 10.1126/science.1228456 ec_funded: 1 intvolume: ' 339' issue: '6117' language: - iso: eng main_file_link: - open_access: '1' url: https://kops.uni-konstanz.de/bitstream/123456789/26341/2/Weber_263418.pdf month: '01' oa: 1 oa_version: Published Version page: 328 - 332 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes (EU) - _id: 25ABD200-B435-11E9-9278-68D0E5697425 grant_number: RGP0058/2011 name: 'Cell migration in complex environments: from in vivo experiments to theoretical models' publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '3959' quality_controlled: '1' scopus_import: '1' status: public title: Interstitial dendritic cell guidance by haptotactic chemokine gradients type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 339 year: '2013' ... --- _id: '522' abstract: - lang: eng text: Podoplanin, a mucin-like plasma membrane protein, is expressed by lymphatic endothelial cells and responsible for separation of blood and lymphatic circulation through activation of platelets. Here we show that podoplanin is also expressed by thymic fibroblastic reticular cells (tFRC), a novel thymic medulla stroma cell type associated with thymic conduits, and involved in development of natural regulatory T cells (nTreg). Young mice deficient in podoplanin lack nTreg owing to retardation of CD4+CD25+ thymocytes in the cortex and missing differentiation of Foxp3+ thymocytes in the medulla. This might be due to CCL21 that delocalizes upon deletion of the CCL21-binding podoplanin from medullar tFRC to cortex areas. The animals do not remain devoid of nTreg but generate them delayed within the first month resulting in Th2-biased hypergammaglobulinemia but not in the death-causing autoimmune phenotype of Foxp3-deficient Scurfy mice. author: - first_name: Elke full_name: Fuertbauer, Elke last_name: Fuertbauer - first_name: Jan full_name: Zaujec, Jan last_name: Zaujec - first_name: Pavel full_name: Uhrin, Pavel last_name: Uhrin - first_name: Ingrid full_name: Raab, Ingrid last_name: Raab - first_name: Michele full_name: Weber, Michele id: 3A3FC708-F248-11E8-B48F-1D18A9856A87 last_name: Weber - first_name: Helga full_name: Schachner, Helga last_name: Schachner - first_name: Miroslav full_name: Bauer, Miroslav last_name: Bauer - first_name: Gerhard full_name: Schütz, Gerhard last_name: Schütz - first_name: Bernd full_name: Binder, Bernd last_name: Binder - 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: Dontscho full_name: Kerjaschki, Dontscho last_name: Kerjaschki - first_name: Hannes full_name: Stockinger, Hannes last_name: Stockinger citation: ama: Fuertbauer E, Zaujec J, Uhrin P, et al. Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells. Immunology Letters. 2013;154(1-2):31-41. doi:10.1016/j.imlet.2013.07.007 apa: Fuertbauer, E., Zaujec, J., Uhrin, P., Raab, I., Weber, M., Schachner, H., … Stockinger, H. (2013). Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells. Immunology Letters. Elsevier. https://doi.org/10.1016/j.imlet.2013.07.007 chicago: Fuertbauer, Elke, Jan Zaujec, Pavel Uhrin, Ingrid Raab, Michele Weber, Helga Schachner, Miroslav Bauer, et al. “Thymic Medullar Conduits-Associated Podoplanin Promotes Natural Regulatory T Cells.” Immunology Letters. Elsevier, 2013. https://doi.org/10.1016/j.imlet.2013.07.007. ieee: E. Fuertbauer et al., “Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells,” Immunology Letters, vol. 154, no. 1–2. Elsevier, pp. 31–41, 2013. ista: Fuertbauer E, Zaujec J, Uhrin P, Raab I, Weber M, Schachner H, Bauer M, Schütz G, Binder B, Sixt MK, Kerjaschki D, Stockinger H. 2013. Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells. Immunology Letters. 154(1–2), 31–41. mla: Fuertbauer, Elke, et al. “Thymic Medullar Conduits-Associated Podoplanin Promotes Natural Regulatory T Cells.” Immunology Letters, vol. 154, no. 1–2, Elsevier, 2013, pp. 31–41, doi:10.1016/j.imlet.2013.07.007. short: E. Fuertbauer, J. Zaujec, P. Uhrin, I. Raab, M. Weber, H. Schachner, M. Bauer, G. Schütz, B. Binder, M.K. Sixt, D. Kerjaschki, H. Stockinger, Immunology Letters 154 (2013) 31–41. date_created: 2018-12-11T11:46:57Z date_published: 2013-07-01T00:00:00Z date_updated: 2021-01-12T08:01:22Z day: '01' department: - _id: MiSi doi: 10.1016/j.imlet.2013.07.007 intvolume: ' 154' issue: 1-2 language: - iso: eng month: '07' oa_version: None page: 31 - 41 publication: Immunology Letters publication_status: published publisher: Elsevier publist_id: '7300' quality_controlled: '1' scopus_import: 1 status: public title: Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 154 year: '2013' ... --- _id: '10900' abstract: - lang: eng text: Leukocyte migration through the interstitial space is crucial for the maintenance of tolerance and immunity. The main cues for leukocyte trafficking are chemokines thought to directionally guide these cells towards their targets. However, model systems that facilitate quantification of chemokine-guided leukocyte migration in vivo are uncommon. Here we describe an ex vivo crawl-in assay using explanted mouse ears that allows the visualization of chemokine-dependent dendritic cell (DC) motility in the dermal interstitium in real time. We present methods for the preparation of mouse ear sheets and their use in multidimensional confocal imaging experiments to monitor and analyze the directional migration of fluorescently labelled DCs through the dermis and into afferent lymphatic vessels. The assay provides a more physiological approach to study leukocyte migration than in vitro three-dimensional (3D) or 2-dimensional (2D) migration assays such as collagen gels and transwell assays. acknowledgement: We would like to thank Alexander Eichner and Ingrid de Vries for discussion and critical reading of the manuscript, and Mary Frank for assistance with the recording of videos and images in Fig. 1. M.S. is supported through funding from the German Research Foundation (DFG). M.W. acknowledges the Alexander von Humboldt Foundation for funding. alternative_title: - Methods in Molecular Biology article_processing_charge: No author: - first_name: Michele full_name: Weber, Michele id: 3A3FC708-F248-11E8-B48F-1D18A9856A87 last_name: Weber - 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: 'Weber M, Sixt MK. Live Cell Imaging of Chemotactic Dendritic Cell Migration in Explanted Mouse Ear Preparations. In: Cardona A, Ubogu E, eds. Chemokines. Vol 1013. MIMB. Totowa, NJ: Humana Press; 2013:215-226. doi:10.1007/978-1-62703-426-5_14' apa: 'Weber, M., & Sixt, M. K. (2013). Live Cell Imaging of Chemotactic Dendritic Cell Migration in Explanted Mouse Ear Preparations. In A. Cardona & E. Ubogu (Eds.), Chemokines (Vol. 1013, pp. 215–226). Totowa, NJ: Humana Press. https://doi.org/10.1007/978-1-62703-426-5_14' chicago: 'Weber, Michele, and Michael K Sixt. “Live Cell Imaging of Chemotactic Dendritic Cell Migration in Explanted Mouse Ear Preparations.” In Chemokines, edited by Astrid Cardona and Eroboghene Ubogu, 1013:215–26. MIMB. Totowa, NJ: Humana Press, 2013. https://doi.org/10.1007/978-1-62703-426-5_14.' ieee: 'M. Weber and M. K. Sixt, “Live Cell Imaging of Chemotactic Dendritic Cell Migration in Explanted Mouse Ear Preparations,” in Chemokines, vol. 1013, A. Cardona and E. Ubogu, Eds. Totowa, NJ: Humana Press, 2013, pp. 215–226.' ista: 'Weber M, Sixt MK. 2013.Live Cell Imaging of Chemotactic Dendritic Cell Migration in Explanted Mouse Ear Preparations. In: Chemokines. Methods in Molecular Biology, vol. 1013, 215–226.' mla: Weber, Michele, and Michael K. Sixt. “Live Cell Imaging of Chemotactic Dendritic Cell Migration in Explanted Mouse Ear Preparations.” Chemokines, edited by Astrid Cardona and Eroboghene Ubogu, vol. 1013, Humana Press, 2013, pp. 215–26, doi:10.1007/978-1-62703-426-5_14. short: M. Weber, M.K. Sixt, in:, A. Cardona, E. Ubogu (Eds.), Chemokines, Humana Press, Totowa, NJ, 2013, pp. 215–226. date_created: 2022-03-21T07:47:41Z date_published: 2013-04-03T00:00:00Z date_updated: 2023-09-05T13:15:33Z day: '03' department: - _id: MiSi doi: 10.1007/978-1-62703-426-5_14 editor: - first_name: Astrid full_name: Cardona, Astrid last_name: Cardona - first_name: Eroboghene full_name: Ubogu, Eroboghene last_name: Ubogu external_id: pmid: - '23625502' intvolume: ' 1013' language: - iso: eng month: '04' oa_version: None page: 215-226 place: Totowa, NJ pmid: 1 publication: Chemokines publication_identifier: eisbn: - '9781627034265' eissn: - 1940-6029 isbn: - '9781627034258' issn: - 1064-3745 publication_status: published publisher: Humana Press quality_controlled: '1' scopus_import: '1' series_title: MIMB status: public title: Live Cell Imaging of Chemotactic Dendritic Cell Migration in Explanted Mouse Ear Preparations type: book_chapter user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 1013 year: '2013' ... --- _id: '3167' article_type: letter_note author: - first_name: Michele full_name: Weber, Michele id: 3A3FC708-F248-11E8-B48F-1D18A9856A87 last_name: Weber citation: ama: Weber M. NextGen speaks 13 . Science. 2012;336(6077):32-34. doi:10.1126/science.336.6077.32 apa: Weber, M. (2012). NextGen speaks 13 . Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.336.6077.32 chicago: Weber, Michele. “NextGen Speaks 13 .” Science. American Association for the Advancement of Science, 2012. https://doi.org/10.1126/science.336.6077.32. ieee: M. Weber, “NextGen speaks 13 ,” Science, vol. 336, no. 6077. American Association for the Advancement of Science, pp. 32–34, 2012. ista: Weber M. 2012. NextGen speaks 13 . Science. 336(6077), 32–34. mla: Weber, Michele. “NextGen Speaks 13 .” Science, vol. 336, no. 6077, American Association for the Advancement of Science, 2012, pp. 32–34, doi:10.1126/science.336.6077.32. short: M. Weber, Science 336 (2012) 32–34. date_created: 2018-12-11T12:01:47Z date_published: 2012-04-06T00:00:00Z date_updated: 2021-01-12T07:41:32Z day: '06' department: - _id: MiSi doi: 10.1126/science.336.6077.32 external_id: pmid: - '22491839' intvolume: ' 336' issue: '6077' language: - iso: eng month: '04' oa_version: None page: 32-34 pmid: 1 popular_science: '1' publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '3516' status: public title: 'NextGen speaks 13 ' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 336 year: '2012' ... --- _id: '3960' abstract: - lang: eng text: When lymphocytes follow chemotactic cues, they can adopt different migratory modes depending on the geometry and molecular composition of their extracellular environment. In this issue of The EMBO Journal, Klemke et al (2010) describe a novel Ras-dependent chemokine receptor signalling pathway that leads to activation of cofilin, which in turn amplifies actin turnover. This signalling module is exclusively required for lymphocyte migration in three-dimensional (3D) environments, but not for locomotion on two-dimensional (2D) surfaces. author: - first_name: Michele full_name: Michele Weber id: 3A3FC708-F248-11E8-B48F-1D18A9856A87 last_name: Weber - first_name: Michael K full_name: Michael Sixt id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 citation: ama: Weber M, Sixt MK. MEK signalling tunes actin treadmilling for interstitial lymphocyte migration. EMBO Journal. 2010;29(17):2861-2863. doi:10.1038/emboj.2010.183 apa: Weber, M., & Sixt, M. K. (2010). MEK signalling tunes actin treadmilling for interstitial lymphocyte migration. EMBO Journal. Wiley-Blackwell. https://doi.org/10.1038/emboj.2010.183 chicago: Weber, Michele, and Michael K Sixt. “MEK Signalling Tunes Actin Treadmilling for Interstitial Lymphocyte Migration.” EMBO Journal. Wiley-Blackwell, 2010. https://doi.org/10.1038/emboj.2010.183. ieee: M. Weber and M. K. Sixt, “MEK signalling tunes actin treadmilling for interstitial lymphocyte migration,” EMBO Journal, vol. 29, no. 17. Wiley-Blackwell, pp. 2861–2863, 2010. ista: Weber M, Sixt MK. 2010. MEK signalling tunes actin treadmilling for interstitial lymphocyte migration. EMBO Journal. 29(17), 2861–2863. mla: Weber, Michele, and Michael K. Sixt. “MEK Signalling Tunes Actin Treadmilling for Interstitial Lymphocyte Migration.” EMBO Journal, vol. 29, no. 17, Wiley-Blackwell, 2010, pp. 2861–63, doi:10.1038/emboj.2010.183. short: M. Weber, M.K. Sixt, EMBO Journal 29 (2010) 2861–2863. date_created: 2018-12-11T12:06:07Z date_published: 2010-09-01T00:00:00Z date_updated: 2021-01-12T07:53:29Z day: '01' doi: 10.1038/emboj.2010.183 extern: 1 intvolume: ' 29' issue: '17' main_file_link: - open_access: '1' url: http://www.ncbi.nlm.nih.gov/pmc/issues/190105/ month: '09' oa: 1 page: 2861 - 2863 publication: EMBO Journal publication_status: published publisher: Wiley-Blackwell publist_id: '2167' quality_controlled: 0 status: public title: MEK signalling tunes actin treadmilling for interstitial lymphocyte migration type: journal_article volume: 29 year: '2010' ... --- _id: '3954' abstract: - lang: eng text: The leading front of a cell can either protrude as an actin-free membrane bleb that is inflated by actomyosin-driven contractile forces, or as an actin-rich pseudopodium, a site where polymerizing actin filaments push out the membrane. Pushing filaments can only cause the membrane to protrude if the expanding actin network experiences a retrograde counter-force, which is usually provided by transmembrane receptors of the integrin family. Here we show that chemotactic dendritic cells mechanically adapt to the adhesive properties of their substrate by switching between integrin-mediated and integrin-independent locomotion. We found that on engaging the integrin-actin clutch, actin polymerization was entirely turned into protrusion, whereas on disengagement actin underwent slippage and retrograde flow. Remarkably, accelerated retrograde flow was balanced by an increased actin polymerization rate; therefore, cell shape and protrusion velocity remained constant on alternating substrates. Due to this adaptive response in polymerization dynamics, tracks of adhesive substrate did not dictate the path of the cells. Instead, directional guidance was exclusively provided by a soluble gradient of chemoattractant, which endowed these 'amoeboid' cells with extraordinary flexibility, enabling them to traverse almost every type of tissue. acknowledgement: We thank S. Cremer for statistical analysis, K. Hirsch for technical assistance, D. Critchley for talin1-deficient mice and R. Fässler for integrindeficient mice, discussions and critical reading of the manuscript. This work was supported by the German Research Foundation, the Peter Hans Hofschneider Foundation for Experimental Biomedicine, the Max Planck Society, the Alexander von Humboldt Foundation and the allergology programme of the Landesstiftung Baden-Württemberg. author: - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Kathrin full_name: Schumann, Kathrin id: F44D762E-4F9D-11E9-B64C-9EB26CEFFB5F last_name: Schumann - first_name: Michele full_name: Weber, Michele id: 3A3FC708-F248-11E8-B48F-1D18A9856A87 last_name: Weber - first_name: Tim full_name: Lämmermann, Tim last_name: Lämmermann - first_name: Holger full_name: Pflicke, Holger last_name: Pflicke - first_name: Matthieu full_name: Piel, Matthieu last_name: Piel - first_name: Julien full_name: Polleux, Julien last_name: Polleux - first_name: Joachim full_name: Spatz, Joachim last_name: Spatz - 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: Renkawitz J, Schumann K, Weber M, et al. Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. 2009;11(12):1438-1443. doi:10.1038/ncb1992 apa: Renkawitz, J., Schumann, K., Weber, M., Lämmermann, T., Pflicke, H., Piel, M., … Sixt, M. K. (2009). Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. Nature Publishing Group. https://doi.org/10.1038/ncb1992 chicago: Renkawitz, Jörg, Kathrin Schumann, Michele Weber, Tim Lämmermann, Holger Pflicke, Matthieu Piel, Julien Polleux, Joachim Spatz, and Michael K Sixt. “Adaptive Force Transmission in Amoeboid Cell Migration.” Nature Cell Biology. Nature Publishing Group, 2009. https://doi.org/10.1038/ncb1992. ieee: J. Renkawitz et al., “Adaptive force transmission in amoeboid cell migration,” Nature Cell Biology, vol. 11, no. 12. Nature Publishing Group, pp. 1438–1443, 2009. ista: Renkawitz J, Schumann K, Weber M, Lämmermann T, Pflicke H, Piel M, Polleux J, Spatz J, Sixt MK. 2009. Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. 11(12), 1438–1443. mla: Renkawitz, Jörg, et al. “Adaptive Force Transmission in Amoeboid Cell Migration.” Nature Cell Biology, vol. 11, no. 12, Nature Publishing Group, 2009, pp. 1438–43, doi:10.1038/ncb1992. short: J. Renkawitz, K. Schumann, M. Weber, T. Lämmermann, H. Pflicke, M. Piel, J. Polleux, J. Spatz, M.K. Sixt, Nature Cell Biology 11 (2009) 1438–1443. date_created: 2018-12-11T12:06:05Z date_published: 2009-11-15T00:00:00Z date_updated: 2021-01-12T07:53:27Z day: '15' doi: 10.1038/ncb1992 extern: '1' intvolume: ' 11' issue: '12' language: - iso: eng month: '11' oa_version: None page: 1438 - 1443 publication: Nature Cell Biology publication_status: published publisher: Nature Publishing Group publist_id: '2173' status: public title: Adaptive force transmission in amoeboid cell migration type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 11 year: '2009' ...