1. Acto-myosin force organization modulates centriole separation and PLK4 recruitment to ensure centriole fidelity
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Helder Maiato, Irène Wang, Amel Mettouchi, Jorge G Ferreira, Philippe Moreau, Elisa Vitiello, Martial Balland, Vanessa Nunes, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chromosome Instability and Dynamics Laboratory, Universidade do Porto-Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Toxines bactériennes - Bacterial Toxins, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), This work was funded by grants from the ANR, Arc, PHC-Pessoa Campus France/Fundação para a Ciência e Tecnologia, FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/BEX-BCM/1758/2014 (POCI-01–0145-FEDER-016589). This work has been partially supported by the LabeX Tec 21 (Investissements d’Avenir: grant agreement No. ANR-11-LABX-0030)., ANR-11-LABX-0030,TEC XXI,Ingénierie de la Complexité : la mécanique et ses interfaces au service des enjeux sociétaux du 21iè(2011), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Universidade do Porto [Porto]-Instituto de Biologia Molecular e Celular, Universidade do Porto [Porto], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0030/11-LABX-0030,TEC XXI,Ingénierie de la Complexité : la mécanique et ses interfaces au service des enjeux sociétaux du 21iè(2011), Instituto de Investigação e Inovação em Saúde, Universidade do Porto = University of Porto-Instituto de Biologia Molecular e Celular, Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Matière et Systèmes Complexes (MSC)
- Subjects
0301 basic medicine ,Intravital Microscopy ,Centriole ,General Physics and Astronomy ,02 engineering and technology ,Myosin ,Thymidine / pharmacology ,Time-Lapse Imaging / methods ,lcsh:Science ,Actins / metabolism ,Centrioles ,Microscopy, Confocal ,Multidisciplinary ,Cell Cycle ,Centriole duplication ,021001 nanoscience & nanotechnology ,Cell biology ,0210 nano-technology ,PLK4 ,Cell Cycle / physiology ,Science ,[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] ,macromolecular substances ,Myosins ,Protein Serine-Threonine Kinases ,Biology ,Cell Cycle / drug effects ,Time-Lapse Imaging ,Article ,General Biochemistry, Genetics and Molecular Biology ,Centrioles / physiology ,Myosins / physiology ,03 medical and health sciences ,Centrioles / metabolism ,Humans ,Centrosome duplication ,Myosins / metabolism ,Actins / physiology ,Protein-Serine-Threonine Kinases / physiology ,General Chemistry ,Aneuploidy ,Actins ,030104 developmental biology ,Centrosome ,Intravital Microscopy / methods ,lcsh:Q ,Protein-Serine-Threonine Kinases / metabolism ,HeLa Cells ,Thymidine - Abstract
The presence of aberrant number of centrioles is a recognized cause of aneuploidy and hallmark of cancer. Hence, centriole duplication needs to be tightly regulated. It has been proposed that centriole separation limits centrosome duplication. The mechanism driving centriole separation is poorly understood and little is known on how this is linked to centriole duplication. Here, we propose that actin-generated forces regulate centriole separation. By imposing geometric constraints via micropatterns, we were able to prove that precise acto-myosin force arrangements control direction, distance and time of centriole separation. Accordingly, inhibition of acto-myosin contractility impairs centriole separation. Alongside, we observed that organization of acto-myosin force modulates specifically the length of S-G2 phases of the cell cycle, PLK4 recruitment at the centrosome and centriole fidelity. These discoveries led us to suggest that acto-myosin forces might act in fundamental mechanisms of aneuploidy prevention., Centriolar separation is thought to be crucial for centriole duplication, but the mechanism behind separation is poorly understood. Here, using micropatterning, the authors report that actomyosin forces influence the direction, distance, and time of centriole separation.
- Published
- 2019
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