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CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes

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  • Dalileh Nabi

    (Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
    Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Hauke Drechsler

    (B CUBE-Center for Molecular Bioengineering, Technische Universität Dresden)

  • Johannes Pschirer

    (Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden)

  • Franz Korn

    (Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden)

  • Nadine Schuler

    (Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden)

  • Stefan Diez

    (B CUBE-Center for Molecular Bioengineering, Technische Universität Dresden
    Cluster of Excellence Physics of Life, Technische Universität Dresden
    Max Planck Institute of Molecular Cell Biology and Genetics)

  • Rolf Jessberger

    (Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden)

  • Mariola Chacón

    (Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden
    CABIMER, Centro Andaluz de Biología Molecular & Medicina Regenerativa)

Abstract

Proper chromosome segregation is essential to avoid aneuploidy, yet this process fails with increasing age in mammalian oocytes. Here we report a role for the scarcely described protein CENP-V in oocyte spindle formation and chromosome segregation. We show that depending on the oocyte maturation state, CENP-V localizes to centromeres, to microtubule organizing centers, and to spindle microtubules. We find that Cenp-V−/− oocytes feature severe deficiencies, including metaphase I arrest, strongly reduced polar body extrusion, increased numbers of mis-aligned chromosomes and aneuploidy, multipolar spindles, unfocused spindle poles and loss of kinetochore spindle fibres. We also show that CENP-V protein binds, diffuses along, and bundles microtubules in vitro. The spindle assembly checkpoint arrests about half of metaphase I Cenp-V−/− oocytes from young adults only. This finding suggests checkpoint weakening in ageing oocytes, which mature despite carrying mis-aligned chromosomes. Thus, CENP-V is a microtubule bundling protein crucial to faithful oocyte meiosis, and Cenp-V−/− oocytes reveal age-dependent weakening of the spindle assembly checkpoint.

Suggested Citation

  • Dalileh Nabi & Hauke Drechsler & Johannes Pschirer & Franz Korn & Nadine Schuler & Stefan Diez & Rolf Jessberger & Mariola Chacón, 2021. "CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26826-3
    DOI: 10.1038/s41467-021-26826-3
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    References listed on IDEAS

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    1. Dean Clift & Melina Schuh, 2015. "A three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    2. Janko Kajtez & Anastasia Solomatina & Maja Novak & Bruno Polak & Kruno Vukušić & Jonas Rüdiger & Gheorghe Cojoc & Ana Milas & Ivana Šumanovac Šestak & Patrik Risteski & Federica Tavano & Anna H. Klemm, 2016. "Overlap microtubules link sister k-fibres and balance the forces on bi-oriented kinetochores," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
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