Protecting centrosomes from fracturing enables efficient cell navigation
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.
Authors
- Janina Kroll (ORCID: https://orcid.org/0000-0002-2209-4808)
- Jörg Renkawitz (ORCID: https://orcid.org/0000-0003-2856-3369)
- Robert Hauschild (ORCID: https://orcid.org/0000-0001-9843-3522)
- Jingyuan Cheng (ORCID: https://orcid.org/0000-0001-8942-0607)
- Jack Merrin (ORCID: https://orcid.org/0000-0001-5145-4609)
- Germán Camargo Ortega (ORCID: https://orcid.org/0000-0002-4305-2578)
- Shaunak Ghosh (ORCID: https://orcid.org/0000-0002-8760-715X)
- Madeleine T. Schmitt
- Petra Kameritsch (ORCID: https://orcid.org/0000-0002-9824-4323)
- Andreas W. Thomae (ORCID: https://orcid.org/0000-0003-3156-9075)
- Thomas Penz
- Christoph Bock (ORCID: https://orcid.org/0000-0001-6091-3088)
- Tobias Straub (ORCID: https://orcid.org/0000-0002-0547-0453)
- Luisa Bach (ORCID: https://orcid.org/0000-0002-3476-6325)
- Eva Kiermaier (ORCID: https://orcid.org/0000-0001-6165-5738)
- Felix Meissner (ORCID: https://orcid.org/0000-0003-1000-7989)
- Dirk Baumjohann (ORCID: https://orcid.org/0000-0001-8385-8288)
- Mauricio J. A. Ruiz‐Fernandez (ORCID: https://orcid.org/0000-0001-9693-1317)
- Jana Pachlopnik Schmid (ORCID: https://orcid.org/0000-0002-6653-9047)
- Kasia Stefanowski
- Peter Konopka (ORCID: https://orcid.org/0009-0002-2373-2653)
- Gamze Naz Öztan
Institutions
- University of Bonn (DE)
- Austrian Academy of Sciences (AT)
- Institute of Science and Technology Austria (AT)
- Austrian Research Institute for Artificial Intelligence (AT)
- University Hospital Bonn (DE)
- Helmholtz Zentrum München (DE)
- CeMM Research Center for Molecular Medicine (AT)
- Centre of Experimental Medicine of the Slovak Academy of Sciences (SK)
- Life & Brain (Germany) (DE)
- Medical University of Vienna (AT)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Science Advances
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1126/sciadv.adx4047
- Citations
- 5
- Primary Topic
- Cellular Mechanics and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 5.76