--- _id: '9094' abstract: - lang: eng text: Dendritic cells (DCs) are crucial for the priming of naive T cells and the initiation of adaptive immunity. Priming is initiated at a heterologous cell–cell contact, the immunological synapse (IS). While it is established that F-actin dynamics regulates signaling at the T cell side of the contact, little is known about the cytoskeletal contribution on the DC side. Here, we show that the DC actin cytoskeleton is decisive for the formation of a multifocal synaptic structure, which correlates with T cell priming efficiency. DC actin at the IS appears in transient foci that are dynamized by the WAVE regulatory complex (WRC). The absence of the WRC in DCs leads to stabilized contacts with T cells, caused by an increase in ICAM1-integrin–mediated cell–cell adhesion. This results in lower numbers of activated and proliferating T cells, demonstrating an important role for DC actin in the regulation of immune synapse functionality. article_number: e202006081 article_processing_charge: No article_type: original author: - 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: LM full_name: Altenburger, LM last_name: Altenburger - first_name: R full_name: Hauschild, R last_name: Hauschild - first_name: Frank P full_name: Assen, Frank P id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87 last_name: Assen orcid: 0000-0003-3470-6119 - first_name: K full_name: Rottner, K last_name: Rottner - first_name: Stradal full_name: TEB, Stradal last_name: TEB - first_name: A full_name: Diz-Muñoz, A last_name: Diz-Muñoz - first_name: JV full_name: Stein, JV 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: Leithner AF, Altenburger L, Hauschild R, et al. Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. Journal of Cell Biology. 2021;220(4). doi:10.1083/jcb.202006081 apa: Leithner, A. F., Altenburger, L., Hauschild, R., Assen, F. P., Rottner, K., TEB, S., … Sixt, M. K. (2021). Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.202006081 chicago: Leithner, Alexander F, LM Altenburger, R Hauschild, Frank P Assen, K Rottner, Stradal TEB, A Diz-Muñoz, JV Stein, and Michael K Sixt. “Dendritic Cell Actin Dynamics Control Contact Duration and Priming Efficiency at the Immunological Synapse.” Journal of Cell Biology. Rockefeller University Press, 2021. https://doi.org/10.1083/jcb.202006081. ieee: A. F. Leithner et al., “Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse,” Journal of Cell Biology, vol. 220, no. 4. Rockefeller University Press, 2021. ista: Leithner AF, Altenburger L, Hauschild R, Assen FP, Rottner K, TEB S, Diz-Muñoz A, Stein J, Sixt MK. 2021. Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse. Journal of Cell Biology. 220(4), e202006081. mla: Leithner, Alexander F., et al. “Dendritic Cell Actin Dynamics Control Contact Duration and Priming Efficiency at the Immunological Synapse.” Journal of Cell Biology, vol. 220, no. 4, e202006081, Rockefeller University Press, 2021, doi:10.1083/jcb.202006081. short: A.F. Leithner, L. Altenburger, R. Hauschild, F.P. Assen, K. Rottner, S. TEB, A. Diz-Muñoz, J. Stein, M.K. Sixt, Journal of Cell Biology 220 (2021). date_created: 2021-02-05T10:08:04Z date_published: 2021-04-05T00:00:00Z date_updated: 2023-09-05T13:57:53Z day: '05' ddc: - '570' department: - _id: MiSi doi: 10.1083/jcb.202006081 external_id: isi: - '000626365700001' pmid: - '33533935' file: - access_level: open_access checksum: 843ebc153847c8626e13c9c5ce71d533 content_type: application/pdf creator: dernst date_created: 2022-05-12T14:16:21Z date_updated: 2022-05-12T14:16:21Z file_id: '11367' file_name: 2021_JournCellBiology_Leithner.pdf file_size: 5102328 relation: main_file success: 1 file_date_updated: 2022-05-12T14:16:21Z has_accepted_license: '1' intvolume: ' 220' isi: 1 issue: '4' language: - iso: eng month: '04' 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' scopus_import: '1' status: public title: Dendritic cell actin dynamics control contact duration and priming efficiency at the immunological synapse 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 220 year: '2021' ... --- _id: '9429' abstract: - lang: eng text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs. acknowledged_ssus: - _id: PreCl acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27). article_number: '3058' article_processing_charge: No article_type: original author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Georgi A full_name: Dimchev, Georgi A id: 38C393BE-F248-11E8-B48F-1D18A9856A87 last_name: Dimchev orcid: 0000-0001-8370-6161 - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Caroline full_name: Kreuzinger, Caroline id: 382077BA-F248-11E8-B48F-1D18A9856A87 last_name: Kreuzinger - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Zoe full_name: Dobler, Zoe id: D23090A2-9057-11EA-883A-A8396FC7A38F last_name: Dobler - first_name: Emanuele full_name: Cacci, Emanuele last_name: Cacci - first_name: Florian KM full_name: Schur, Florian KM id: 48AD8942-F248-11E8-B48F-1D18A9856A87 last_name: Schur orcid: 0000-0003-4790-8078 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x. ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021. ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058. mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x. short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021). date_created: 2021-05-28T11:49:46Z date_published: 2021-05-24T00:00:00Z date_updated: 2024-03-28T23:30:23Z day: '24' ddc: - '572' department: - _id: GaNo - _id: JoDa - _id: FlSc - _id: MiSi - _id: LifeSc - _id: Bio doi: 10.1038/s41467-021-23123-x ec_funded: 1 external_id: isi: - '000658769900010' file: - access_level: open_access checksum: 337e0f7959c35ec959984cacdcb472ba content_type: application/pdf creator: kschuh date_created: 2021-05-28T12:39:43Z date_updated: 2021-05-28T12:39:43Z file_id: '9430' file_name: 2021_NatureCommunications_Morandell.pdf file_size: 9358599 relation: main_file success: 1 file_date_updated: 2021-05-28T12:39:43Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '1' keyword: - General Biochemistry - Genetics and Molecular Biology language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 25444568-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715508' name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F07807 name: Neural stem cells in autism and epilepsy - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: press_release url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/ record: - id: '7800' relation: earlier_version status: public - id: '12401' relation: dissertation_contains status: public status: public title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development 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: '10307' abstract: - lang: eng text: Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response. acknowledged_ssus: - _id: LifeSc - _id: Bio - _id: PreCl - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Kathrin full_name: Tomasek, Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek orcid: 0000-0003-3768-877X citation: ama: Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021. doi:10.15479/at:ista:10307 apa: Tomasek, K. (2021). Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10307 chicago: Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10307. ieee: K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,” Institute of Science and Technology Austria, 2021. ista: Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response. Institute of Science and Technology Austria. mla: Tomasek, Kathrin. Pathogenic Escherichia Coli Hijack the Host Immune Response. Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307. short: K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response, Institute of Science and Technology Austria, 2021. date_created: 2021-11-18T15:05:06Z date_published: 2021-11-18T00:00:00Z date_updated: 2023-09-07T13:34:38Z day: '18' ddc: - '570' degree_awarded: PhD department: - _id: MiSi - _id: CaGu - _id: GradSch doi: 10.15479/at:ista:10307 file: - access_level: open_access checksum: b39c9e0ef18d0484d537a67551effd02 content_type: application/pdf creator: ktomasek date_created: 2021-11-18T15:07:31Z date_updated: 2022-12-20T23:30:05Z embargo: 2022-11-18 file_id: '10308' file_name: ThesisTomasekKathrin.pdf file_size: 13266088 relation: main_file - access_level: closed checksum: c0c440ee9e5ef1102a518a4f9f023e7c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: ktomasek date_created: 2021-11-18T15:07:46Z date_updated: 2022-12-20T23:30:05Z embargo_to: open_access file_id: '10309' file_name: ThesisTomasekKathrin.docx file_size: 7539509 relation: source_file file_date_updated: 2022-12-20T23:30:05Z has_accepted_license: '1' language: - iso: eng month: '11' oa: 1 oa_version: Published Version page: '73' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '10316' 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: 0000-0002-4561-241X - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 title: Pathogenic Escherichia coli hijack the host immune response type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2021' ... --- _id: '10316' abstract: - lang: eng text: A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease. acknowledged_ssus: - _id: Bio - _id: PreCl - _id: EM-Fac acknowledgement: We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S. article_processing_charge: No author: - first_name: Kathrin full_name: Tomasek, Kathrin id: 3AEC8556-F248-11E8-B48F-1D18A9856A87 last_name: Tomasek orcid: 0000-0003-3768-877X - 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: Ivana full_name: Glatzová, Ivana id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d last_name: Glatzová - first_name: Michael S. full_name: Lukesch, Michael S. last_name: Lukesch - 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 citation: ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv. doi:10.1101/2021.10.18.464770 apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., & Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2021.10.18.464770 chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770. ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory. ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, 10.1101/2021.10.18.464770. mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2021.10.18.464770. short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.). date_created: 2021-11-19T12:24:16Z date_published: 2021-10-18T00:00:00Z date_updated: 2024-03-28T23:30:35Z day: '18' department: - _id: CaGu - _id: MiSi doi: 10.1101/2021.10.18.464770 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1 month: '10' oa: 1 oa_version: Preprint project: - _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 publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '11843' relation: later_version status: public - id: '10307' relation: dissertation_contains status: public status: public title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14 type: preprint user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2021' ... --- _id: '7234' abstract: - lang: eng text: T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin‐related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F‐actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3‐knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon‐like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three‐dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3‐dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities. article_processing_charge: No article_type: original author: - first_name: Peyman full_name: Obeidy, Peyman last_name: Obeidy - first_name: Lining A. full_name: Ju, Lining A. last_name: Ju - first_name: Stefan H. full_name: Oehlers, Stefan H. last_name: Oehlers - first_name: Nursafwana S. full_name: Zulkhernain, Nursafwana S. last_name: Zulkhernain - first_name: Quintin full_name: Lee, Quintin last_name: Lee - first_name: Jorge L. full_name: Galeano Niño, Jorge L. last_name: Galeano Niño - first_name: Rain Y.Q. full_name: Kwan, Rain Y.Q. last_name: Kwan - first_name: Shweta full_name: Tikoo, Shweta last_name: Tikoo - first_name: Lois L. full_name: Cavanagh, Lois L. last_name: Cavanagh - first_name: Paulus full_name: Mrass, Paulus last_name: Mrass - first_name: Adam J.L. full_name: Cook, Adam J.L. last_name: Cook - first_name: Shaun P. full_name: Jackson, Shaun P. last_name: Jackson - first_name: Maté full_name: Biro, Maté last_name: Biro - first_name: Ben full_name: Roediger, Ben last_name: Roediger - 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: Wolfgang full_name: Weninger, Wolfgang last_name: Weninger citation: ama: Obeidy P, Ju LA, Oehlers SH, et al. Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology. 2020;98(2):93-113. doi:10.1111/imcb.12304 apa: Obeidy, P., Ju, L. A., Oehlers, S. H., Zulkhernain, N. S., Lee, Q., Galeano Niño, J. L., … Weninger, W. (2020). Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology. Wiley. https://doi.org/10.1111/imcb.12304 chicago: Obeidy, Peyman, Lining A. Ju, Stefan H. Oehlers, Nursafwana S. Zulkhernain, Quintin Lee, Jorge L. Galeano Niño, Rain Y.Q. Kwan, et al. “Partial Loss of Actin Nucleator Actin-Related Protein 2/3 Activity Triggers Blebbing in Primary T Lymphocytes.” Immunology and Cell Biology. Wiley, 2020. https://doi.org/10.1111/imcb.12304. ieee: P. Obeidy et al., “Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes,” Immunology and Cell Biology, vol. 98, no. 2. Wiley, pp. 93–113, 2020. ista: Obeidy P, Ju LA, Oehlers SH, Zulkhernain NS, Lee Q, Galeano Niño JL, Kwan RYQ, Tikoo S, Cavanagh LL, Mrass P, Cook AJL, Jackson SP, Biro M, Roediger B, Sixt MK, Weninger W. 2020. Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes. Immunology and Cell Biology. 98(2), 93–113. mla: Obeidy, Peyman, et al. “Partial Loss of Actin Nucleator Actin-Related Protein 2/3 Activity Triggers Blebbing in Primary T Lymphocytes.” Immunology and Cell Biology, vol. 98, no. 2, Wiley, 2020, pp. 93–113, doi:10.1111/imcb.12304. short: P. Obeidy, L.A. Ju, S.H. Oehlers, N.S. Zulkhernain, Q. Lee, J.L. Galeano Niño, R.Y.Q. Kwan, S. Tikoo, L.L. Cavanagh, P. Mrass, A.J.L. Cook, S.P. Jackson, M. Biro, B. Roediger, M.K. Sixt, W. Weninger, Immunology and Cell Biology 98 (2020) 93–113. date_created: 2020-01-05T23:00:48Z date_published: 2020-02-01T00:00:00Z date_updated: 2023-08-17T14:21:12Z day: '01' ddc: - '570' department: - _id: MiSi doi: 10.1111/imcb.12304 external_id: isi: - '000503885600001' pmid: - '31698518' file: - access_level: open_access checksum: c389477b4b52172ef76afff8a06c6775 content_type: application/pdf creator: dernst date_created: 2020-11-19T11:22:33Z date_updated: 2020-11-19T11:22:33Z file_id: '8775' file_name: 2020_ImmunologyCellBio_Obeidy.pdf file_size: 8569945 relation: main_file success: 1 file_date_updated: 2020-11-19T11:22:33Z has_accepted_license: '1' intvolume: ' 98' isi: 1 issue: '2' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: 93-113 pmid: 1 publication: Immunology and Cell Biology publication_identifier: eissn: - '14401711' issn: - '08189641' publication_status: published publisher: Wiley quality_controlled: '1' scopus_import: '1' status: public title: Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes 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: 98 year: '2020' ... --- _id: '7623' abstract: - lang: eng text: A two-dimensional mathematical model for cells migrating without adhesion capabilities is presented and analyzed. Cells are represented by their cortex, which is modeled as an elastic curve, subject to an internal pressure force. Net polymerization or depolymerization in the cortex is modeled via local addition or removal of material, driving a cortical flow. The model takes the form of a fully nonlinear degenerate parabolic system. An existence analysis is carried out by adapting ideas from the theory of gradient flows. Numerical simulations show that these simple rules can account for the behavior observed in experiments, suggesting a possible mechanical mechanism for adhesion-independent motility. acknowledgement: This work has been supported by the Vienna Science and Technology Fund, Grant no. LS13-029. G.J. and C.S. also acknowledge support by the Austrian Science Fund, Grants no. W1245, F 65, and W1261, as well as by the Fondation Sciences Mathématiques de Paris, and by Paris-Sciences-et-Lettres. article_processing_charge: No article_type: original author: - first_name: Gaspard full_name: Jankowiak, Gaspard last_name: Jankowiak - first_name: Diane full_name: Peurichard, Diane last_name: Peurichard - first_name: Anne full_name: Reversat, Anne id: 35B76592-F248-11E8-B48F-1D18A9856A87 last_name: Reversat orcid: 0000-0003-0666-8928 - first_name: Christian full_name: Schmeiser, Christian last_name: Schmeiser - 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: Jankowiak G, Peurichard D, Reversat A, Schmeiser C, Sixt MK. Modeling adhesion-independent cell migration. Mathematical Models and Methods in Applied Sciences. 2020;30(3):513-537. doi:10.1142/S021820252050013X apa: Jankowiak, G., Peurichard, D., Reversat, A., Schmeiser, C., & Sixt, M. K. (2020). Modeling adhesion-independent cell migration. Mathematical Models and Methods in Applied Sciences. World Scientific. https://doi.org/10.1142/S021820252050013X chicago: Jankowiak, Gaspard, Diane Peurichard, Anne Reversat, Christian Schmeiser, and Michael K Sixt. “Modeling Adhesion-Independent Cell Migration.” Mathematical Models and Methods in Applied Sciences. World Scientific, 2020. https://doi.org/10.1142/S021820252050013X. ieee: G. Jankowiak, D. Peurichard, A. Reversat, C. Schmeiser, and M. K. Sixt, “Modeling adhesion-independent cell migration,” Mathematical Models and Methods in Applied Sciences, vol. 30, no. 3. World Scientific, pp. 513–537, 2020. ista: Jankowiak G, Peurichard D, Reversat A, Schmeiser C, Sixt MK. 2020. Modeling adhesion-independent cell migration. Mathematical Models and Methods in Applied Sciences. 30(3), 513–537. mla: Jankowiak, Gaspard, et al. “Modeling Adhesion-Independent Cell Migration.” Mathematical Models and Methods in Applied Sciences, vol. 30, no. 3, World Scientific, 2020, pp. 513–37, doi:10.1142/S021820252050013X. short: G. Jankowiak, D. Peurichard, A. Reversat, C. Schmeiser, M.K. Sixt, Mathematical Models and Methods in Applied Sciences 30 (2020) 513–537. date_created: 2020-03-31T11:25:05Z date_published: 2020-03-18T00:00:00Z date_updated: 2023-08-18T10:18:56Z day: '18' department: - _id: MiSi doi: 10.1142/S021820252050013X external_id: arxiv: - '1903.09426' isi: - '000525349900003' intvolume: ' 30' isi: 1 issue: '3' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1903.09426 month: '03' oa: 1 oa_version: Preprint page: 513-537 project: - _id: 25AD6156-B435-11E9-9278-68D0E5697425 grant_number: LS13-029 name: Modeling of Polarization and Motility of Leukocytes in Three-Dimensional Environments publication: Mathematical Models and Methods in Applied Sciences publication_identifier: issn: - '02182025' publication_status: published publisher: World Scientific quality_controlled: '1' scopus_import: '1' status: public title: Modeling adhesion-independent cell migration type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 30 year: '2020' ... --- _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 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: '7876' abstract: - lang: eng text: 'In contrast to lymph nodes, the lymphoid regions of the spleen—the white pulp—are located deep within the organ, yielding the trafficking paths of T cells in the white pulp largely invisible. In an intravital microscopy tour de force reported in this issue of Immunity, Chauveau et al. show that T cells perform unidirectional, perivascular migration through the enigmatic marginal zone bridging channels. ' article_processing_charge: No article_type: original author: - 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: Tim full_name: Lämmermann, Tim last_name: Lämmermann citation: ama: 'Sixt MK, Lämmermann T. T cells: Bridge-and-channel commute to the white pulp. Immunity. 2020;52(5):721-723. doi:10.1016/j.immuni.2020.04.020' apa: 'Sixt, M. K., & Lämmermann, T. (2020). T cells: Bridge-and-channel commute to the white pulp. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2020.04.020' chicago: 'Sixt, Michael K, and Tim Lämmermann. “T Cells: Bridge-and-Channel Commute to the White Pulp.” Immunity. Elsevier, 2020. https://doi.org/10.1016/j.immuni.2020.04.020.' ieee: 'M. K. Sixt and T. Lämmermann, “T cells: Bridge-and-channel commute to the white pulp,” Immunity, vol. 52, no. 5. Elsevier, pp. 721–723, 2020.' ista: 'Sixt MK, Lämmermann T. 2020. T cells: Bridge-and-channel commute to the white pulp. Immunity. 52(5), 721–723.' mla: 'Sixt, Michael K., and Tim Lämmermann. “T Cells: Bridge-and-Channel Commute to the White Pulp.” Immunity, vol. 52, no. 5, Elsevier, 2020, pp. 721–23, doi:10.1016/j.immuni.2020.04.020.' short: M.K. Sixt, T. Lämmermann, Immunity 52 (2020) 721–723. date_created: 2020-05-24T22:00:57Z date_published: 2020-05-19T00:00:00Z date_updated: 2023-08-21T06:27:18Z day: '19' department: - _id: MiSi doi: 10.1016/j.immuni.2020.04.020 external_id: isi: - '000535371100002' intvolume: ' 52' isi: 1 issue: '5' language: - iso: eng main_file_link: - open_access: '1' url: https://pure.mpg.de/pubman/item/item_3265599_2/component/file_3265620/Sixt%20et%20al..pdf month: '05' oa: 1 oa_version: Published Version page: 721-723 publication: Immunity publication_identifier: eissn: - '10974180' issn: - '10747613' publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'T cells: Bridge-and-channel commute to the white pulp' type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 52 year: '2020' ... --- _id: '7909' abstract: - lang: eng text: Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration. article_number: e55351 article_processing_charge: No article_type: original author: - first_name: Julia full_name: Damiano-Guercio, Julia last_name: Damiano-Guercio - first_name: Laëtitia full_name: Kurzawa, Laëtitia last_name: Kurzawa - first_name: Jan full_name: Müller, Jan id: AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D last_name: Müller - first_name: Georgi A full_name: Dimchev, Georgi A id: 38C393BE-F248-11E8-B48F-1D18A9856A87 last_name: Dimchev orcid: 0000-0001-8370-6161 - first_name: Matthias full_name: Schaks, Matthias last_name: Schaks - first_name: Maria full_name: Nemethova, Maria id: 34E27F1C-F248-11E8-B48F-1D18A9856A87 last_name: Nemethova - first_name: Thomas full_name: Pokrant, Thomas last_name: Pokrant - first_name: Stefan full_name: Brühmann, Stefan last_name: Brühmann - first_name: Joern full_name: Linkner, Joern last_name: Linkner - first_name: Laurent full_name: Blanchoin, Laurent last_name: Blanchoin - 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: Klemens full_name: Rottner, Klemens last_name: Rottner - first_name: Jan full_name: Faix, Jan last_name: Faix citation: ama: Damiano-Guercio J, Kurzawa L, Müller J, et al. Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion. eLife. 2020;9. doi:10.7554/eLife.55351 apa: Damiano-Guercio, J., Kurzawa, L., Müller, J., Dimchev, G. A., Schaks, M., Nemethova, M., … Faix, J. (2020). Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.55351 chicago: Damiano-Guercio, Julia, Laëtitia Kurzawa, Jan Müller, Georgi A Dimchev, Matthias Schaks, Maria Nemethova, Thomas Pokrant, et al. “Loss of Ena/VASP Interferes with Lamellipodium Architecture, Motility and Integrin-Dependent Adhesion.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.55351. ieee: J. Damiano-Guercio et al., “Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion,” eLife, vol. 9. eLife Sciences Publications, 2020. ista: Damiano-Guercio J, Kurzawa L, Müller J, Dimchev GA, Schaks M, Nemethova M, Pokrant T, Brühmann S, Linkner J, Blanchoin L, Sixt MK, Rottner K, Faix J. 2020. Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion. eLife. 9, e55351. mla: Damiano-Guercio, Julia, et al. “Loss of Ena/VASP Interferes with Lamellipodium Architecture, Motility and Integrin-Dependent Adhesion.” ELife, vol. 9, e55351, eLife Sciences Publications, 2020, doi:10.7554/eLife.55351. short: J. Damiano-Guercio, L. Kurzawa, J. Müller, G.A. Dimchev, M. Schaks, M. Nemethova, T. Pokrant, S. Brühmann, J. Linkner, L. Blanchoin, M.K. Sixt, K. Rottner, J. Faix, ELife 9 (2020). date_created: 2020-05-31T22:00:49Z date_published: 2020-05-11T00:00:00Z date_updated: 2023-08-21T06:32:25Z day: '11' ddc: - '570' department: - _id: MiSi doi: 10.7554/eLife.55351 ec_funded: 1 external_id: isi: - '000537208000001' file: - access_level: open_access checksum: d33bd4441b9a0195718ce1ba5d2c48a6 content_type: application/pdf creator: dernst date_created: 2020-06-02T10:35:37Z date_updated: 2020-07-14T12:48:05Z file_id: '7914' file_name: 2020_eLife_Damiano_Guercio.pdf file_size: 10535713 relation: main_file file_date_updated: 2020-07-14T12:48:05Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 25FE9508-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '724373' name: Cellular navigation along spatial gradients publication: eLife publication_identifier: eissn: - 2050084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion 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: 9 year: '2020' ... --- _id: '8132' abstract: - lang: eng text: The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia. Hem1−/− mice display systemic autoimmunity, phenocopying the human disease. In the absence of Hem1, B cells become deprived of extracellular stimuli necessary to maintain the strength of B cell receptor signaling at a level permissive for survival of non-autoreactive B cells. This shifts the balance of B cell fate choices toward autoreactive B cells and thus autoimmunity. article_number: eabc3979 article_processing_charge: No article_type: original author: - first_name: Elisabeth full_name: Salzer, Elisabeth last_name: Salzer - first_name: Samaneh full_name: Zoghi, Samaneh last_name: Zoghi - first_name: Máté G. full_name: Kiss, Máté G. last_name: Kiss - first_name: Frieda full_name: Kage, Frieda last_name: Kage - first_name: Christina full_name: Rashkova, Christina last_name: Rashkova - first_name: Stephanie full_name: Stahnke, Stephanie last_name: Stahnke - first_name: Matthias full_name: Haimel, Matthias last_name: Haimel - first_name: René full_name: Platzer, René last_name: Platzer - first_name: Michael full_name: Caldera, Michael last_name: Caldera - first_name: Rico Chandra full_name: Ardy, Rico Chandra last_name: Ardy - first_name: Birgit full_name: Hoeger, Birgit last_name: Hoeger - first_name: Jana full_name: Block, Jana last_name: Block - first_name: David full_name: Medgyesi, David last_name: Medgyesi - first_name: Celine full_name: Sin, Celine last_name: Sin - first_name: Sepideh full_name: Shahkarami, Sepideh last_name: Shahkarami - first_name: Renate full_name: Kain, Renate last_name: Kain - first_name: Vahid full_name: Ziaee, Vahid last_name: Ziaee - first_name: Peter full_name: Hammerl, Peter last_name: Hammerl - first_name: Christoph full_name: Bock, Christoph last_name: Bock - first_name: Jörg full_name: Menche, Jörg last_name: Menche - first_name: Loïc full_name: Dupré, Loïc last_name: Dupré - first_name: Johannes B. full_name: Huppa, Johannes B. last_name: Huppa - 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: Alexis full_name: Lomakin, Alexis last_name: Lomakin - first_name: Klemens full_name: Rottner, Klemens last_name: Rottner - first_name: Christoph J. full_name: Binder, Christoph J. last_name: Binder - first_name: Theresia E.B. full_name: Stradal, Theresia E.B. last_name: Stradal - first_name: Nima full_name: Rezaei, Nima last_name: Rezaei - first_name: Kaan full_name: Boztug, Kaan last_name: Boztug citation: ama: Salzer E, Zoghi S, Kiss MG, et al. The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity. Science Immunology. 2020;5(49). doi:10.1126/sciimmunol.abc3979 apa: Salzer, E., Zoghi, S., Kiss, M. G., Kage, F., Rashkova, C., Stahnke, S., … Boztug, K. (2020). The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity. Science Immunology. AAAS. https://doi.org/10.1126/sciimmunol.abc3979 chicago: Salzer, Elisabeth, Samaneh Zoghi, Máté G. Kiss, Frieda Kage, Christina Rashkova, Stephanie Stahnke, Matthias Haimel, et al. “The Cytoskeletal Regulator HEM1 Governs B Cell Development and Prevents Autoimmunity.” Science Immunology. AAAS, 2020. https://doi.org/10.1126/sciimmunol.abc3979. ieee: E. Salzer et al., “The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity,” Science Immunology, vol. 5, no. 49. AAAS, 2020. ista: Salzer E, Zoghi S, Kiss MG, Kage F, Rashkova C, Stahnke S, Haimel M, Platzer R, Caldera M, Ardy RC, Hoeger B, Block J, Medgyesi D, Sin C, Shahkarami S, Kain R, Ziaee V, Hammerl P, Bock C, Menche J, Dupré L, Huppa JB, Sixt MK, Lomakin A, Rottner K, Binder CJ, Stradal TEB, Rezaei N, Boztug K. 2020. The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity. Science Immunology. 5(49), eabc3979. mla: Salzer, Elisabeth, et al. “The Cytoskeletal Regulator HEM1 Governs B Cell Development and Prevents Autoimmunity.” Science Immunology, vol. 5, no. 49, eabc3979, AAAS, 2020, doi:10.1126/sciimmunol.abc3979. short: E. Salzer, S. Zoghi, M.G. Kiss, F. Kage, C. Rashkova, S. Stahnke, M. Haimel, R. Platzer, M. Caldera, R.C. Ardy, B. Hoeger, J. Block, D. Medgyesi, C. Sin, S. Shahkarami, R. Kain, V. Ziaee, P. Hammerl, C. Bock, J. Menche, L. Dupré, J.B. Huppa, M.K. Sixt, A. Lomakin, K. Rottner, C.J. Binder, T.E.B. Stradal, N. Rezaei, K. Boztug, Science Immunology 5 (2020). date_created: 2020-07-19T22:00:58Z date_published: 2020-07-10T00:00:00Z date_updated: 2023-08-22T07:56:04Z day: '10' department: - _id: MiSi doi: 10.1126/sciimmunol.abc3979 external_id: isi: - '000546994600004' pmid: - '32646852' intvolume: ' 5' isi: 1 issue: '49' language: - iso: eng month: '07' oa_version: None pmid: 1 publication: Science Immunology publication_identifier: eissn: - '24709468' publication_status: published publisher: AAAS quality_controlled: '1' scopus_import: '1' status: public title: The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 5 year: '2020' ...