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Schmitt, M.T.* ; Kroll, J.* ; Ruiz-Fernandez, M.J.A.* ; Hauschild, R.* ; Ghosh, S.* ; Kameritsch, P.* ; Merrin, J.* ; Schmid, J.* ; Stefanowski, K.* ; Thomae, A.W.* ; Cheng, J.* ; Öztan, G.N.* ; Konopka, P.* ; Camargo Ortega, G. ; Penz, T.* ; Bach, L.* ; Baumjohann, D.* ; Bock, C.* ; Straub, T.* ; Meissner, F.* ; Kiermaier, E.* ; Renkawitz, J.*

Protecting centrosomes from fracturing enables efficient cell navigation.

Sci. Adv. 11:eadx4047 (2025)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Leukocyte Migration; Microtubules; Centriole; Visualization; Nucleation; Interacts; Protein; Repair; C-nap1
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 11, Issue: 17, Pages: , Article Number: eadx4047 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
Grants CZI
German Research Foundation
LMU Institutional Strategy LMU-Excellent within the framework of the German Excellence Initiative
Medical & Clinician Scientist Program (McSP) lMU Munich
Deutsche Forschungsgemeinschaft (DFG
German Research Foundation) under Germany's Excellence Strategy
German Research Foundation) Grossgeraeteantrag
Germany's Excellence Strategy
RA Life and Health (University of Bonn) as part of the Excellence Strategy of the federal and state governments
Peter Hans Hofschneider Professorship of the Stiftung Experimentelle Biomedizin