--- _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 license: https://creativecommons.org/licenses/by-nc-nd/4.0/ 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: '7875' abstract: - lang: eng text: 'Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.' acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: PreCl acknowledgement: "The authors thank the Scientific Service Units (Life Sciences, Bioimaging, Preclinical) of the Institute of Science and Technology Austria for excellent support. This work was funded by the European Research Council (ERC StG 281556 and CoG 724373), two grants from the Austrian\r\nScience Fund (FWF; P29911 and DK Nanocell W1250-B20 to M. Sixt) and by the German Research Foundation (DFG SFB1032 project B09) to O. Thorn-Seshold and D. Trauner. J. Renkawitz was supported by ISTFELLOW funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under the Research Executive Agency grant agreement (291734) and a European Molecular Biology Organization long-term fellowship (ALTF 1396-2014) co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409), E. Kiermaier by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2151—390873048, and H. Hacker by the American Lebanese Syrian Associated ¨Charities. K.-D. Fischer was supported by the Analysis, Imaging and Modelling of Neuronal and Inflammatory Processes graduate school funded by the Ministry of Economics, Science, and Digitisation of the State Saxony-Anhalt and by the European Funds for Social and Regional Development." article_number: e201907154 article_processing_charge: No article_type: original author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Irute full_name: Girkontaite, Irute last_name: Girkontaite - first_name: Kerry full_name: Tedford, Kerry last_name: Tedford - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Oliver full_name: Thorn-Seshold, Oliver last_name: Thorn-Seshold - first_name: Dirk full_name: Trauner, Dirk id: E8F27F48-3EBA-11E9-92A1-B709E6697425 last_name: Trauner - first_name: Hans full_name: Häcker, Hans last_name: Häcker - first_name: Klaus Dieter full_name: Fischer, Klaus Dieter last_name: Fischer - first_name: Eva full_name: Kiermaier, Eva id: 3EB04B78-F248-11E8-B48F-1D18A9856A87 last_name: Kiermaier orcid: 0000-0001-6165-5738 - 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: Kopf A, Renkawitz J, Hauschild R, et al. Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. 2020;219(6). doi:10.1083/jcb.201907154 apa: Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin, J., … Sixt, M. K. (2020). Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.201907154 chicago: Kopf, Aglaja, Jörg Renkawitz, Robert Hauschild, Irute Girkontaite, Kerry Tedford, Jack Merrin, Oliver Thorn-Seshold, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” The Journal of Cell Biology. Rockefeller University Press, 2020. https://doi.org/10.1083/jcb.201907154. ieee: A. Kopf et al., “Microtubules control cellular shape and coherence in amoeboid migrating cells,” The Journal of Cell Biology, vol. 219, no. 6. Rockefeller University Press, 2020. ista: Kopf A, Renkawitz J, Hauschild R, Girkontaite I, Tedford K, Merrin J, Thorn-Seshold O, Trauner D, Häcker H, Fischer KD, Kiermaier E, Sixt MK. 2020. Microtubules control cellular shape and coherence in amoeboid migrating cells. The Journal of Cell Biology. 219(6), e201907154. mla: Kopf, Aglaja, et al. “Microtubules Control Cellular Shape and Coherence in Amoeboid Migrating Cells.” The Journal of Cell Biology, vol. 219, no. 6, e201907154, Rockefeller University Press, 2020, doi:10.1083/jcb.201907154. short: A. Kopf, J. Renkawitz, R. Hauschild, I. Girkontaite, K. Tedford, J. Merrin, O. Thorn-Seshold, D. Trauner, H. Häcker, K.D. Fischer, E. Kiermaier, M.K. Sixt, The Journal of Cell Biology 219 (2020). date_created: 2020-05-24T22:00:56Z date_published: 2020-06-01T00:00:00Z date_updated: 2023-08-21T06:28:17Z day: '01' ddc: - '570' department: - _id: MiSi - _id: Bio - _id: NanoFab doi: 10.1083/jcb.201907154 ec_funded: 1 external_id: isi: - '000538141100020' pmid: - '32379884' file: - access_level: open_access checksum: cb0b9c77842ae1214caade7b77e4d82d content_type: application/pdf creator: dernst date_created: 2020-11-24T13:25:13Z date_updated: 2020-11-24T13:25:13Z file_id: '8801' file_name: 2020_JCellBiol_Kopf.pdf file_size: 7536712 relation: main_file success: 1 file_date_updated: 2020-11-24T13:25:13Z has_accepted_license: '1' intvolume: ' 219' isi: 1 issue: '6' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '06' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 26018E70-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29911 name: Mechanical adaptation of lamellipodial actin - _id: 252C3B08-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W 1250-B20 name: Nano-Analytics of Cellular Systems - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 25A48D24-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1396-2014 name: Molecular and system level view of immune cell migration publication: The Journal of Cell Biology publication_identifier: eissn: - 1540-8140 publication_status: published publisher: Rockefeller University Press quality_controlled: '1' scopus_import: '1' status: public title: Microtubules control cellular shape and coherence in amoeboid migrating cells 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: 219 year: '2020' ... --- _id: '8142' abstract: - lang: eng text: Cell production and differentiation for the acquisition of specific functions are key features of living systems. The dynamic network of cellular microtubules provides the necessary platform to accommodate processes associated with the transition of cells through the individual phases of cytogenesis. Here, we show that the plant hormone cytokinin fine‐tunes the activity of the microtubular cytoskeleton during cell differentiation and counteracts microtubular rearrangements driven by the hormone auxin. The endogenous upward gradient of cytokinin activity along the longitudinal growth axis in Arabidopsis thaliana roots correlates with robust rearrangements of the microtubule cytoskeleton in epidermal cells progressing from the proliferative to the differentiation stage. Controlled increases in cytokinin activity result in premature re‐organization of the microtubule network from transversal to an oblique disposition in cells prior to their differentiation, whereas attenuated hormone perception delays cytoskeleton conversion into a configuration typical for differentiated cells. Intriguingly, cytokinin can interfere with microtubules also in animal cells, such as leukocytes, suggesting that a cytokinin‐sensitive control pathway for the microtubular cytoskeleton may be at least partially conserved between plant and animal cells. acknowledged_ssus: - _id: Bio - _id: LifeSc acknowledgement: We thank Takashi Aoyama, David Alabadi, and Bert De Rybel for sharing material, Jiří Friml, Maciek Adamowski, and Katerina Schwarzerová for inspiring discussions, and Martine De Cock for help in preparing the manuscript. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by the Bioimaging Facility (BIF), especially to Robert Hauschild; and the Life Science Facility (LSF). J.C.M. is the recipient of a EMBO Long‐Term Fellowship (ALTF number 710‐2016). This work was supported with MEYS CR, project no.CZ.02.1.01/0.0/0.0/16_019/0000738 to J.P., and by the Austrian Science Fund (FWF01_I1774S) to E.B. article_number: e104238 article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Juan C full_name: Montesinos López, Juan C id: 310A8E3E-F248-11E8-B48F-1D18A9856A87 last_name: Montesinos López orcid: 0000-0001-9179-6099 - first_name: A full_name: Abuzeineh, A last_name: Abuzeineh - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Alba full_name: Juanes Garcia, Alba id: 40F05888-F248-11E8-B48F-1D18A9856A87 last_name: Juanes Garcia orcid: 0000-0002-1009-9652 - first_name: Krisztina full_name: Ötvös, Krisztina id: 29B901B0-F248-11E8-B48F-1D18A9856A87 last_name: Ötvös orcid: 0000-0002-5503-4983 - first_name: J full_name: Petrášek, J last_name: Petrášek - 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: Eva full_name: Benková, Eva id: 38F4F166-F248-11E8-B48F-1D18A9856A87 last_name: Benková orcid: 0000-0002-8510-9739 citation: ama: Montesinos López JC, Abuzeineh A, Kopf A, et al. Phytohormone cytokinin guides microtubule dynamics during cell progression from proliferative to differentiated stage. The Embo Journal. 2020;39(17). doi:10.15252/embj.2019104238 apa: Montesinos López, J. C., Abuzeineh, A., Kopf, A., Juanes Garcia, A., Ötvös, K., Petrášek, J., … Benková, E. (2020). Phytohormone cytokinin guides microtubule dynamics during cell progression from proliferative to differentiated stage. The Embo Journal. Embo Press. https://doi.org/10.15252/embj.2019104238 chicago: Montesinos López, Juan C, A Abuzeineh, Aglaja Kopf, Alba Juanes Garcia, Krisztina Ötvös, J Petrášek, Michael K Sixt, and Eva Benková. “Phytohormone Cytokinin Guides Microtubule Dynamics during Cell Progression from Proliferative to Differentiated Stage.” The Embo Journal. Embo Press, 2020. https://doi.org/10.15252/embj.2019104238. ieee: J. C. Montesinos López et al., “Phytohormone cytokinin guides microtubule dynamics during cell progression from proliferative to differentiated stage,” The Embo Journal, vol. 39, no. 17. Embo Press, 2020. ista: Montesinos López JC, Abuzeineh A, Kopf A, Juanes Garcia A, Ötvös K, Petrášek J, Sixt MK, Benková E. 2020. Phytohormone cytokinin guides microtubule dynamics during cell progression from proliferative to differentiated stage. The Embo Journal. 39(17), e104238. mla: Montesinos López, Juan C., et al. “Phytohormone Cytokinin Guides Microtubule Dynamics during Cell Progression from Proliferative to Differentiated Stage.” The Embo Journal, vol. 39, no. 17, e104238, Embo Press, 2020, doi:10.15252/embj.2019104238. short: J.C. Montesinos López, A. Abuzeineh, A. Kopf, A. Juanes Garcia, K. Ötvös, J. Petrášek, M.K. Sixt, E. Benková, The Embo Journal 39 (2020). date_created: 2020-07-21T09:08:38Z date_published: 2020-09-01T00:00:00Z date_updated: 2023-09-05T13:05:47Z day: '01' ddc: - '580' department: - _id: MiSi - _id: EvBe doi: 10.15252/embj.2019104238 external_id: isi: - '000548311800001' pmid: - '32667089' file: - access_level: open_access checksum: 43d2b36598708e6ab05c69074e191d57 content_type: application/pdf creator: dernst date_created: 2020-12-02T09:13:23Z date_updated: 2020-12-02T09:13:23Z file_id: '8827' file_name: 2020_EMBO_Montesinos.pdf file_size: 3497156 relation: main_file success: 1 file_date_updated: 2020-12-02T09:13:23Z has_accepted_license: '1' intvolume: ' 39' isi: 1 issue: '17' language: - iso: eng month: '09' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 253E54C8-B435-11E9-9278-68D0E5697425 grant_number: ALTF710-2016 name: Molecular mechanism of auxindriven formative divisions delineating lateral root organogenesis in plants - _id: 2542D156-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I 1774-B16 name: Hormone cross-talk drives nutrient dependent plant development publication: The Embo Journal publication_identifier: eissn: - 1460-2075 issn: - 0261-4189 publication_status: published publisher: Embo Press quality_controlled: '1' scopus_import: '1' status: public title: Phytohormone cytokinin guides microtubule dynamics during cell progression from proliferative to differentiated stage 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 39 year: '2020' ... --- _id: '6979' article_processing_charge: No article_type: original author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - 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: 'Kopf A, Sixt MK. Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. Current Biology. 2019;29(20):R1091-R1093. doi:10.1016/j.cub.2019.08.068' apa: 'Kopf, A., & Sixt, M. K. (2019). Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2019.08.068' chicago: 'Kopf, Aglaja, and Michael K Sixt. “Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal.” Current Biology. Cell Press, 2019. https://doi.org/10.1016/j.cub.2019.08.068.' ieee: 'A. Kopf and M. K. Sixt, “Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal,” Current Biology, vol. 29, no. 20. Cell Press, pp. R1091–R1093, 2019.' ista: 'Kopf A, Sixt MK. 2019. Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal. Current Biology. 29(20), R1091–R1093.' mla: 'Kopf, Aglaja, and Michael K. Sixt. “Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal.” Current Biology, vol. 29, no. 20, Cell Press, 2019, pp. R1091–93, doi:10.1016/j.cub.2019.08.068.' short: A. Kopf, M.K. Sixt, Current Biology 29 (2019) R1091–R1093. date_created: 2019-11-04T15:18:29Z date_published: 2019-10-21T00:00:00Z date_updated: 2023-09-05T12:43:43Z day: '21' department: - _id: MiSi doi: 10.1016/j.cub.2019.08.068 external_id: isi: - '000491286200016' pmid: - '31639357' intvolume: ' 29' isi: 1 issue: '20' language: - iso: eng month: '10' oa_version: None page: R1091-R1093 pmid: 1 publication: Current Biology publication_identifier: eissn: - 1879-0445 issn: - 0960-9822 publication_status: published publisher: Cell Press quality_controlled: '1' scopus_import: '1' status: public title: 'Gut homeostasis: Active migration of intestinal epithelial cells in tissue renewal' type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 29 year: '2019' ... --- _id: '6891' abstract: - lang: eng text: "While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 citation: ama: Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:10.15479/AT:ISTA:6891 apa: Kopf, A. (2019). The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6891 chicago: Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6891. ieee: A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019. ista: Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. mla: Kopf, Aglaja. The Implication of Cytoskeletal Dynamics on Leukocyte Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6891. short: A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019. date_created: 2019-09-19T08:19:44Z date_published: 2019-07-24T00:00:00Z date_updated: 2023-10-18T08:49:17Z day: '24' ddc: - '570' degree_awarded: PhD department: - _id: MiSi doi: 10.15479/AT:ISTA:6891 file: - access_level: closed checksum: 00d100d6468e31e583051e0a006b640c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: akopf date_created: 2019-10-15T05:28:42Z date_updated: 2020-10-17T22:30:03Z embargo_to: open_access file_id: '6950' file_name: Kopf_PhD_Thesis.docx file_size: 74735267 relation: source_file - access_level: open_access checksum: 5d1baa899993ae6ca81aebebe1797000 content_type: application/pdf creator: akopf date_created: 2019-10-15T05:28:47Z date_updated: 2020-10-17T22:30:03Z embargo: 2020-10-16 file_id: '6951' file_name: Kopf_PhD_Thesis1.pdf file_size: 52787224 relation: main_file file_date_updated: 2020-10-17T22:30:03Z has_accepted_license: '1' keyword: - cell biology - immunology - leukocyte - migration - microfluidics language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '171' project: - _id: 265E2996-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01250-B20 name: Nano-Analytics of Cellular Systems publication_identifier: eissn: - 2663-337X isbn: - 978-3-99078-002-2 publication_status: published publisher: Institute of Science and Technology Austria related_material: link: - relation: press_release url: https://ist.ac.at/en/news/feeling-like-a-cell/ record: - id: '6328' relation: part_of_dissertation status: public - id: '15' relation: part_of_dissertation status: public - id: '6877' 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: The implication of cytoskeletal dynamics on leukocyte migration type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6328' abstract: - lang: eng text: During metazoan development, immune surveillance and cancer dissemination, cells migrate in complex three-dimensional microenvironments1,2,3. These spaces are crowded by cells and extracellular matrix, generating mazes with differently sized gaps that are typically smaller than the diameter of the migrating cell4,5. Most mesenchymal and epithelial cells and some—but not all—cancer cells actively generate their migratory path using pericellular tissue proteolysis6. By contrast, amoeboid cells such as leukocytes use non-destructive strategies of locomotion7, raising the question how these extremely fast cells navigate through dense tissues. Here we reveal that leukocytes sample their immediate vicinity for large pore sizes, and are thereby able to choose the path of least resistance. This allows them to circumnavigate local obstacles while effectively following global directional cues such as chemotactic gradients. Pore-size discrimination is facilitated by frontward positioning of the nucleus, which enables the cells to use their bulkiest compartment as a mechanical gauge. Once the nucleus and the closely associated microtubule organizing centre pass the largest pore, cytoplasmic protrusions still lingering in smaller pores are retracted. These retractions are coordinated by dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning in front of the microtubule organizing centre is a typical feature of amoeboid migration, our findings link the fundamental organization of cellular polarity to the strategy of locomotion. acknowledged_ssus: - _id: SSU article_processing_charge: No article_type: letter_note author: - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Julian A full_name: Stopp, Julian A id: 489E3F00-F248-11E8-B48F-1D18A9856A87 last_name: Stopp - first_name: Ingrid full_name: de Vries, Ingrid id: 4C7D837E-F248-11E8-B48F-1D18A9856A87 last_name: de Vries - first_name: Meghan K. full_name: Driscoll, Meghan K. last_name: Driscoll - first_name: Jack full_name: Merrin, Jack id: 4515C308-F248-11E8-B48F-1D18A9856A87 last_name: Merrin orcid: 0000-0001-5145-4609 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - first_name: Erik S. full_name: Welf, Erik S. last_name: Welf - first_name: Gaudenz full_name: Danuser, Gaudenz last_name: Danuser - first_name: Reto full_name: Fiolka, Reto last_name: Fiolka - 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, Kopf A, Stopp JA, et al. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 2019;568:546-550. doi:10.1038/s41586-019-1087-5 apa: Renkawitz, J., Kopf, A., Stopp, J. A., de Vries, I., Driscoll, M. K., Merrin, J., … Sixt, M. K. (2019). Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1087-5 chicago: Renkawitz, Jörg, Aglaja Kopf, Julian A Stopp, Ingrid de Vries, Meghan K. Driscoll, Jack Merrin, Robert Hauschild, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” Nature. Springer Nature, 2019. https://doi.org/10.1038/s41586-019-1087-5. ieee: J. Renkawitz et al., “Nuclear positioning facilitates amoeboid migration along the path of least resistance,” Nature, vol. 568. Springer Nature, pp. 546–550, 2019. ista: Renkawitz J, Kopf A, Stopp JA, de Vries I, Driscoll MK, Merrin J, Hauschild R, Welf ES, Danuser G, Fiolka R, Sixt MK. 2019. Nuclear positioning facilitates amoeboid migration along the path of least resistance. Nature. 568, 546–550. mla: Renkawitz, Jörg, et al. “Nuclear Positioning Facilitates Amoeboid Migration along the Path of Least Resistance.” Nature, vol. 568, Springer Nature, 2019, pp. 546–50, doi:10.1038/s41586-019-1087-5. short: J. Renkawitz, A. Kopf, J.A. Stopp, I. de Vries, M.K. Driscoll, J. Merrin, R. Hauschild, E.S. Welf, G. Danuser, R. Fiolka, M.K. Sixt, Nature 568 (2019) 546–550. date_created: 2019-04-17T06:52:28Z date_published: 2019-04-25T00:00:00Z date_updated: 2024-03-27T23:30:39Z day: '25' department: - _id: MiSi - _id: NanoFab - _id: Bio doi: 10.1038/s41586-019-1087-5 ec_funded: 1 external_id: isi: - '000465594200050' pmid: - '30944468' intvolume: ' 568' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/ month: '04' oa: 1 oa_version: Submitted Version page: 546-550 pmid: 1 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: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 265FAEBA-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01250-B20 name: Nano-Analytics of Cellular Systems - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme - _id: 25A48D24-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1396-2014 name: Molecular and system level view of immune cell migration publication: Nature publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/leukocytes-use-their-nucleus-as-a-ruler-to-choose-path-of-least-resistance/ record: - id: '14697' relation: dissertation_contains status: public - id: '6891' relation: dissertation_contains status: public scopus_import: '1' status: public title: Nuclear positioning facilitates amoeboid migration along the path of least resistance type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 568 year: '2019' ... --- _id: '6877' article_processing_charge: No article_type: original author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - 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: Kopf A, Sixt MK. The neural crest pitches in to remove apoptotic debris. Cell. 2019;179(1):51-53. doi:10.1016/j.cell.2019.08.047 apa: Kopf, A., & Sixt, M. K. (2019). The neural crest pitches in to remove apoptotic debris. Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.08.047 chicago: Kopf, Aglaja, and Michael K Sixt. “The Neural Crest Pitches in to Remove Apoptotic Debris.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.08.047. ieee: A. Kopf and M. K. Sixt, “The neural crest pitches in to remove apoptotic debris,” Cell, vol. 179, no. 1. Elsevier, pp. 51–53, 2019. ista: Kopf A, Sixt MK. 2019. The neural crest pitches in to remove apoptotic debris. Cell. 179(1), 51–53. mla: Kopf, Aglaja, and Michael K. Sixt. “The Neural Crest Pitches in to Remove Apoptotic Debris.” Cell, vol. 179, no. 1, Elsevier, 2019, pp. 51–53, doi:10.1016/j.cell.2019.08.047. short: A. Kopf, M.K. Sixt, Cell 179 (2019) 51–53. date_created: 2019-09-15T22:00:46Z date_published: 2019-09-19T00:00:00Z date_updated: 2024-03-27T23:30:40Z day: '19' department: - _id: MiSi doi: 10.1016/j.cell.2019.08.047 external_id: isi: - '000486618500011' pmid: - '31539498' intvolume: ' 179' isi: 1 issue: '1' language: - iso: eng month: '09' oa_version: None page: 51-53 pmid: 1 publication: Cell publication_identifier: eissn: - 1097-4172 issn: - 0092-8674 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '6891' relation: dissertation_contains status: public scopus_import: '1' status: public title: The neural crest pitches in to remove apoptotic debris type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 179 year: '2019' ... --- _id: '15' abstract: - lang: eng text: Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux. acknowledged_ssus: - _id: SSU acknowledgement: This work was funded by grants from the European Research Council (ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S. and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457 and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014). article_processing_charge: No author: - first_name: Miroslav full_name: Hons, Miroslav id: 4167FE56-F248-11E8-B48F-1D18A9856A87 last_name: Hons orcid: 0000-0002-6625-3348 - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 - first_name: Robert full_name: Hauschild, Robert id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87 last_name: Hauschild orcid: 0000-0001-9843-3522 - 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: Florian R full_name: Gärtner, Florian R id: 397A88EE-F248-11E8-B48F-1D18A9856A87 last_name: Gärtner orcid: 0000-0001-6120-3723 - first_name: Jun full_name: Abe, Jun last_name: Abe - first_name: Jörg full_name: Renkawitz, Jörg id: 3F0587C8-F248-11E8-B48F-1D18A9856A87 last_name: Renkawitz orcid: 0000-0003-2856-3369 - first_name: Jens full_name: Stein, Jens last_name: Stein - 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: Hons M, Kopf A, Hauschild R, et al. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 2018;19(6):606-616. doi:10.1038/s41590-018-0109-z apa: Hons, M., Kopf, A., Hauschild, R., Leithner, A. F., Gärtner, F. R., Abe, J., … Sixt, M. K. (2018). Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/s41590-018-0109-z chicago: Hons, Miroslav, Aglaja Kopf, Robert Hauschild, Alexander F Leithner, Florian R Gärtner, Jun Abe, Jörg Renkawitz, Jens Stein, and Michael K Sixt. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology. Nature Publishing Group, 2018. https://doi.org/10.1038/s41590-018-0109-z. ieee: M. Hons et al., “Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells,” Nature Immunology, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018. ista: Hons M, Kopf A, Hauschild R, Leithner AF, Gärtner FR, Abe J, Renkawitz J, Stein J, Sixt MK. 2018. Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells. Nature Immunology. 19(6), 606–616. mla: Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal Migration of T Cells.” Nature Immunology, vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:10.1038/s41590-018-0109-z. short: M. Hons, A. Kopf, R. Hauschild, A.F. Leithner, F.R. Gärtner, J. Abe, J. Renkawitz, J. Stein, M.K. Sixt, Nature Immunology 19 (2018) 606–616. date_created: 2018-12-11T11:44:10Z date_published: 2018-05-18T00:00:00Z date_updated: 2024-03-27T23:30:39Z day: '18' department: - _id: MiSi - _id: Bio doi: 10.1038/s41590-018-0109-z ec_funded: 1 external_id: isi: - '000433041500026' pmid: - '29777221' intvolume: ' 19' isi: 1 issue: '6' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pubmed/29777221 month: '05' oa: 1 oa_version: Published Version page: 606 - 616 pmid: 1 project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients - _id: 260AA4E2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '747687' name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells - _id: 25A48D24-B435-11E9-9278-68D0E5697425 grant_number: ALTF 1396-2014 name: Molecular and system level view of immune cell migration - _id: 25A603A2-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '281556' name: Cytoskeletal force generation and force transduction of migrating leukocytes (EU) publication: Nature Immunology publication_status: published publisher: Nature Publishing Group publist_id: '8040' quality_controlled: '1' related_material: record: - id: '6891' relation: dissertation_contains status: public scopus_import: '1' status: public title: Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 19 year: '2018' ...