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Microtubule plus-end regulation by centriolar cap proteins

Funso E. Ogunmolu, Shoeib Moradi, Vladimir A. Volkov, Chris van Hoorn, Jingchao Wu, Nemo Andrea, Shasha Hua, Kai Jiang, Ioannis Vakonakis, Mia Potočnjak, Franz Herzog, Benoît Gigant, Nikita Gudimchuk, Kelly E. Stecker, Marileen Dogterom, Michel O. Steinmetz, View ORCID ProfileAnna Akhmanova
doi: https://doi.org/10.1101/2021.12.29.474442
Funso E. Ogunmolu
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, the Netherlands
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Shoeib Moradi
2Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Forschungsstrasse 111, Villigen, CH-5232, Switzerland
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Vladimir A. Volkov
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, the Netherlands
3Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, van der Maasweg 9, 2629 HZ, Delft, the Netherlands
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Chris van Hoorn
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, the Netherlands
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Jingchao Wu
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, the Netherlands
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Nemo Andrea
3Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, van der Maasweg 9, 2629 HZ, Delft, the Netherlands
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Shasha Hua
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, the Netherlands
4The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, and Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China
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Kai Jiang
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, the Netherlands
4The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, and Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China
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Ioannis Vakonakis
5Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom
6Lonza Biologics, Lonza Ltd, Lonzastrasse, CH-3930 Visp, Switzerland
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Mia Potočnjak
7Ludwig-Maximilians-Universität München, Munich, Germany
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Franz Herzog
7Ludwig-Maximilians-Universität München, Munich, Germany
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Benoît Gigant
8Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France
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Nikita Gudimchuk
9Lomonosov Moscow State University, Department of Physics, and Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
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Kelly E. Stecker
10Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 CH Utrecht, the Netherlands.
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Marileen Dogterom
3Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, van der Maasweg 9, 2629 HZ, Delft, the Netherlands
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  • For correspondence: m.dogterom@tudelft.nl michel.steinmetz@psi.ch a.akhmanova@uu.nl
Michel O. Steinmetz
2Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Forschungsstrasse 111, Villigen, CH-5232, Switzerland
11University of Basel, Biozentrum, Klingelbergstrasse, Basel, CH-4056, Switzerland
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  • For correspondence: m.dogterom@tudelft.nl michel.steinmetz@psi.ch a.akhmanova@uu.nl
Anna Akhmanova
1Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, the Netherlands
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  • ORCID record for Anna Akhmanova
  • For correspondence: m.dogterom@tudelft.nl michel.steinmetz@psi.ch a.akhmanova@uu.nl
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Abstract

Centrioles are microtubule-based organelles required for the formation of centrosomes and cilia. Centriolar microtubules, unlike their cytosolic counterparts, grow very slowly and are very stable. The complex of centriolar proteins CP110 and CEP97 forms a cap that stabilizes the distal centriole end and prevents its over-elongation. Here, we used in vitro reconstitution assays to show that whereas CEP97 does not interact with microtubules directly, CP110 specifically binds microtubule plus ends, potently blocks their growth and induces microtubule pausing. Cryo-electron tomography indicated that CP110 binds to the luminal side of microtubule plus ends and reduces protofilament peeling. Furthermore, CP110 directly interacts with another centriole biogenesis factor, CPAP/SAS- 4, which tracks growing microtubule plus ends, slows down their growth and prevents catastrophes. CP110 and CPAP synergize in inhibiting plus-end growth, and this synergy depends on their direct binding. Together, our data reveal a molecular mechanism controlling centriolar microtubule plus- end dynamics and centriole biogenesis.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • We have updated the data availability section and corrected a small textual mistake in one supplemental figure.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 20, 2022.
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Microtubule plus-end regulation by centriolar cap proteins
Funso E. Ogunmolu, Shoeib Moradi, Vladimir A. Volkov, Chris van Hoorn, Jingchao Wu, Nemo Andrea, Shasha Hua, Kai Jiang, Ioannis Vakonakis, Mia Potočnjak, Franz Herzog, Benoît Gigant, Nikita Gudimchuk, Kelly E. Stecker, Marileen Dogterom, Michel O. Steinmetz, Anna Akhmanova
bioRxiv 2021.12.29.474442; doi: https://doi.org/10.1101/2021.12.29.474442
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Microtubule plus-end regulation by centriolar cap proteins
Funso E. Ogunmolu, Shoeib Moradi, Vladimir A. Volkov, Chris van Hoorn, Jingchao Wu, Nemo Andrea, Shasha Hua, Kai Jiang, Ioannis Vakonakis, Mia Potočnjak, Franz Herzog, Benoît Gigant, Nikita Gudimchuk, Kelly E. Stecker, Marileen Dogterom, Michel O. Steinmetz, Anna Akhmanova
bioRxiv 2021.12.29.474442; doi: https://doi.org/10.1101/2021.12.29.474442

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