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Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11

Author

Listed:
  • Ivan Zadra

    (The Barcelona Institute of Science and Technology)

  • Senda Jimenez-Delgado

    (The Barcelona Institute of Science and Technology)

  • Miquel Anglada-Girotto

    (The Barcelona Institute of Science and Technology)

  • Carolina Segura-Morales

    (The Barcelona Institute of Science and Technology)

  • Zachary J. Compton

    (The Barcelona Institute of Science and Technology)

  • Carsten Janke

    (Université PSL, CNRS UMR3348
    Université Paris-Saclay, CNRS UMR3348)

  • Luis Serrano

    (The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF)
    ICREA, Pg. Lluis Companys 23)

  • Verena Ruprecht

    (The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF)
    ICREA, Pg. Lluis Companys 23)

  • Isabelle Vernos

    (The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF)
    ICREA, Pg. Lluis Companys 23)

Abstract

Regulation of microtubule (MT) dynamics is key for mitotic spindle assembly and faithful chromosome segregation. Here we show that polyglutamylation, a still understudied post-translational modification of spindle MTs, is essential to define their dynamics within the range required for error-free chromosome segregation. We identify TTLL11 as an enzyme driving MT polyglutamylation in mitosis and show that reducing TTLL11 levels in human cells or zebrafish embryos compromises chromosome segregation fidelity and impairs early embryonic development. Our data reveal a mechanism to ensure genome stability in normal cells that is compromised in cancer cells that systematically downregulate TTLL11. Our data suggest a direct link between MT dynamics regulation, MT polyglutamylation and two salient features of tumour cells, aneuploidy and chromosome instability (CIN).

Suggested Citation

  • Ivan Zadra & Senda Jimenez-Delgado & Miquel Anglada-Girotto & Carolina Segura-Morales & Zachary J. Compton & Carsten Janke & Luis Serrano & Verena Ruprecht & Isabelle Vernos, 2022. "Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34909-y
    DOI: 10.1038/s41467-022-34909-y
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    References listed on IDEAS

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    1. Torben Johann Hausrat & Philipp C. Janiesch & Petra Breiden & David Lutz & Sabine Hoffmeister-Ullerich & Irm Hermans-Borgmeyer & Antonio Virgilio Failla & Matthias Kneussel, 2022. "Disruption of tubulin-alpha4a polyglutamylation prevents aggregation of hyper-phosphorylated tau and microglia activation in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
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