Protecting centrosomes from fracturing enables efficient cell navigation

Schmitt MT, Kroll J, Ruiz-Fernandez MJ, 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)

Publication Type: Journal article

Publication year: 2025

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 11

Article Number: eadx4047

Journal Issue: 17

DOI: 10.1126/sciadv.adx4047

Abstract

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.

Involved external institutions

Klinikum der Universität München DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Institute of Science and Technology Austria (IST Austria) AT Austria (AT) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) CeMM Research Center for Molecular Medicine (CeMM) AT Austria (AT) Universitätsklinikum Bonn DE Germany (DE)

How to cite

APA:

Schmitt, M.T., Kroll, J., Ruiz-Fernandez, M.J., Hauschild, R., Ghosh, S., Kameritsch, P.,... Renkawitz, J. (2025). Protecting centrosomes from fracturing enables efficient cell navigation. Science Advances, 11(17). https://doi.org/10.1126/sciadv.adx4047

MLA:

Schmitt, Madeleine T., et al. "Protecting centrosomes from fracturing enables efficient cell navigation." Science Advances 11.17 (2025).

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