---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '19663'
abstract:
- lang: eng
  text: The centrosome is a microtubule orchestrator, nucleating and anchoring microtubules
    that grow radially and exert forces on cargos. At the same time, mechanical stresses
    from the microenvironment and cellular shape changes compress and bend microtubules.
    Yet, centrosomes are membraneless organelles, raising the question of how centrosomes
    withstand mechanical forces. Here, we discover that centrosomes can deform and
    even fracture. We reveal that centrosomes experience deformations during navigational
    pathfinding within motile cells. Coherence of the centrosome is maintained by
    Dyrk3 and cNAP1, preventing fracturing by forces. While cells can compensate for
    the depletion of centriolar-based centrosomes, the fracturing of centrosomes impedes
    cellular function by generating coexisting microtubule organizing centers that
    compete during path navigation and thereby cause cellular entanglement in the
    microenvironment. Our findings show that cells actively maintain the integrity
    of the centrosome to withstand mechanical forces. These results suggest that centrosome
    stability preservation is fundamental, given that almost all cells in multicellular
    organisms experience forces.
acknowledgement: "We thank L. Pelkmans and D. Dormann for providing Dyrk3-EGFP plasmids;
  M. Heuzé for providing a RFP-Pericentrin plasmid; T. Balla for providing a PH-Akt-GFP
  plasmid; E. Snaar-Jagalska for providing a pLenti-V6.3 Ultra-Chili plasmid; T. Tang
  for providing CEP120 a plasmid; D. Trono for providing pMD2.G and psSPAX2 plasmids;
  M. Sixt for providing EB3-mCherry and EMTB-mCherry plasmids as well as 3T3 fibroblasts,
  Lifeact-GFP Hoxb8 cells, and LX293 cells; M. Duggan for RNA isolation from migrating
  DCs; M. Schuster from the Biomedical Sequencing Facility at CeMM; J. Schwarz for
  providing Jurkat T cells; M. Götz for initial transcriptome analysis; M. Götz and
  F. Merino for discussion and sharing reagents; F. Gärtner for discussions and support;
  M. Benjamin Braun for critical reading of the manuscript; and the Core Facility
  Bioimaging, the Core Facility Flow Cytometry, and the Animal Core Facility of the
  Biomedical Center (BMC) for excellent support.\r\nThis work was supported by Peter
  Hans Hofschneider Professorship of the Stiftung Experimentelle Biomedizin (J.R.);
  German Research Foundation grant “CRC914, project A12” (J.R); German Research Foundation
  grant “SPP2332, project 492014049” (J.R.); LMU Institutional Strategy LMU-Excellent
  within the framework of the German Excellence Initiative (J.R.); Medical & Clinician
  Scientist Program (MCSP) LMU Munich (J.K.); Deutsche Forschungsgemeinschaft (DFG;
  German Research Foundation) under Germany’s Excellence Strategy – EXC2151 – 390873048
  (D.B.); Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) Grossgeräteantrag
  457838313 and under Germany’s Excellence Strategy – EXC 2151 – 390873048 (E.K.);
  Ministry of Innovation, Science and Research of North-Rhine-Westphalia (fellowship
  AZ: 421-8.03.03.02-137069) (E.K.); TRA Life and Health (University of Bonn) as part
  of the Excellence Strategy of the federal and state governments (E.K.); and CZI
  grant DAF2020-225401 and grant (DOI https://doi.org/10.37921/120055ratwvi) from
  the Chan Zuckerberg Initiative DAF (R.H.)."
article_number: eadx4047
article_processing_charge: Yes
article_type: original
author:
- first_name: Madeleine T.
  full_name: Schmitt, Madeleine T.
  last_name: Schmitt
- first_name: Janina
  full_name: Kroll, Janina
  last_name: Kroll
- first_name: Mauricio J.A.
  full_name: Ruiz-Fernandez, Mauricio J.A.
  last_name: Ruiz-Fernandez
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Shaunak
  full_name: Ghosh, Shaunak
  last_name: Ghosh
- first_name: Petra
  full_name: Kameritsch, Petra
  last_name: Kameritsch
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Johanna
  full_name: Schmid, Johanna
  last_name: Schmid
- first_name: Kasia
  full_name: Stefanowski, Kasia
  last_name: Stefanowski
- first_name: Andreas W.
  full_name: Thomae, Andreas W.
  last_name: Thomae
- first_name: Jingyuan
  full_name: Cheng, Jingyuan
  last_name: Cheng
- first_name: Gamze Naz
  full_name: Öztan, Gamze Naz
  last_name: Öztan
- first_name: Peter
  full_name: Konopka, Peter
  last_name: Konopka
- first_name: Germán Camargo
  full_name: Ortega, Germán Camargo
  last_name: Ortega
- first_name: Thomas
  full_name: Penz, Thomas
  last_name: Penz
- first_name: Luisa
  full_name: Bach, Luisa
  last_name: Bach
- first_name: Dirk
  full_name: Baumjohann, Dirk
  last_name: Baumjohann
- first_name: Christoph
  full_name: Bock, Christoph
  last_name: Bock
- first_name: Tobias
  full_name: Straub, Tobias
  last_name: Straub
- first_name: Felix
  full_name: Meissner, Felix
  last_name: Meissner
- first_name: Eva
  full_name: Kiermaier, Eva
  id: 3EB04B78-F248-11E8-B48F-1D18A9856A87
  last_name: Kiermaier
  orcid: 0000-0001-6165-5738
- first_name: Jörg
  full_name: Renkawitz, Jörg
  id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
  last_name: Renkawitz
  orcid: 0000-0003-2856-3369
citation:
  ama: Schmitt MT, Kroll J, Ruiz-Fernandez MJA, et al. Protecting centrosomes from
    fracturing enables efficient cell navigation. <i>Science Advances</i>. 2025;11(17).
    doi:<a href="https://doi.org/10.1126/sciadv.adx4047">10.1126/sciadv.adx4047</a>
  apa: Schmitt, M. T., Kroll, J., Ruiz-Fernandez, M. J. A., Hauschild, R., Ghosh,
    S., Kameritsch, P., … Renkawitz, J. (2025). Protecting centrosomes from fracturing
    enables efficient cell navigation. <i>Science Advances</i>. AAAS. <a href="https://doi.org/10.1126/sciadv.adx4047">https://doi.org/10.1126/sciadv.adx4047</a>
  chicago: Schmitt, Madeleine T., Janina Kroll, Mauricio J.A. Ruiz-Fernandez, Robert
    Hauschild, Shaunak Ghosh, Petra Kameritsch, Jack Merrin, et al. “Protecting Centrosomes
    from Fracturing Enables Efficient Cell Navigation.” <i>Science Advances</i>. AAAS,
    2025. <a href="https://doi.org/10.1126/sciadv.adx4047">https://doi.org/10.1126/sciadv.adx4047</a>.
  ieee: M. T. Schmitt <i>et al.</i>, “Protecting centrosomes from fracturing enables
    efficient cell navigation,” <i>Science Advances</i>, vol. 11, no. 17. AAAS, 2025.
  ista: Schmitt MT, Kroll J, Ruiz-Fernandez MJA, Hauschild R, Ghosh S, Kameritsch
    P, Merrin J, Schmid J, Stefanowski K, Thomae AW, Cheng J, Öztan GN, Konopka P,
    Ortega GC, Penz T, Bach L, Baumjohann D, Bock C, Straub T, Meissner F, Kiermaier
    E, Renkawitz J. 2025. Protecting centrosomes from fracturing enables efficient
    cell navigation. Science Advances. 11(17), eadx4047.
  mla: Schmitt, Madeleine T., et al. “Protecting Centrosomes from Fracturing Enables
    Efficient Cell Navigation.” <i>Science Advances</i>, vol. 11, no. 17, eadx4047,
    AAAS, 2025, doi:<a href="https://doi.org/10.1126/sciadv.adx4047">10.1126/sciadv.adx4047</a>.
  short: M.T. Schmitt, J. Kroll, M.J.A. Ruiz-Fernandez, R. Hauschild, S. Ghosh, P.
    Kameritsch, J. Merrin, J. Schmid, K. Stefanowski, A.W. Thomae, J. Cheng, G.N.
    Öztan, P. Konopka, G.C. Ortega, T. Penz, L. Bach, D. Baumjohann, C. Bock, T. Straub,
    F. Meissner, E. Kiermaier, J. Renkawitz, Science Advances 11 (2025).
date_created: 2025-05-11T22:02:38Z
date_published: 2025-04-25T00:00:00Z
date_updated: 2025-09-30T12:26:21Z
day: '25'
ddc:
- '570'
department:
- _id: Bio
- _id: NanoFab
doi: 10.1126/sciadv.adx4047
external_id:
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language:
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license: https://creativecommons.org/licenses/by/4.0/
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473
  grant_number: CZI01
  name: Tools for automation and feedback microscopy
publication: Science Advances
publication_identifier:
  eissn:
  - 2375-2548
publication_status: published
publisher: AAAS
quality_controlled: '1'
scopus_import: '1'
status: public
title: Protecting centrosomes from fracturing enables efficient cell navigation
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