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Protein phosphatase 1 inactivates Mps1 to ensure efficient spindle assembly checkpoint silencing

  1. Margarida Moura
  2. Mariana Osswald
  3. Nelson Leça
  4. João Barbosa
  5. António J Pereira
  6. Helder Maiato
  7. Claudio E Sunkel  Is a corresponding author
  8. Carlos Conde  Is a corresponding author
  1. i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
Research Article
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Cite this article as: eLife 2017;6:e25366 doi: 10.7554/eLife.25366

Abstract

Faithfull genome partitioning during cell division relies on the Spindle Assembly Checkpoint (SAC), a conserved signaling pathway that delays anaphase onset until all chromosomes are attached to spindle microtubules. Mps1 kinase is an upstream SAC regulator that promotes the assembly of an anaphase inhibitor through a sequential multi-target phosphorylation cascade. Thus, the SAC is highly responsive to Mps1, whose activity peaks in early mitosis as a result of its T-loop autophosphorylation. However, the mechanism controlling Mps1 inactivation once kinetochores attach to microtubules and the SAC is satisfied remains unknown. Here we show in vitro and in Drosophila that Protein Phosphatase 1 (PP1) inactivates Mps1 by dephosphorylating its T-loop. PP1-mediated dephosphorylation of Mps1 occurs at kinetochores and in the cytosol, and inactivation of both pools of Mps1 during metaphase is essential to ensure prompt and efficient SAC silencing. Overall, our findings uncover a mechanism of SAC inactivation required for timely mitotic exit.

Article and author information

Author details

  1. Margarida Moura

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  2. Mariana Osswald

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  3. Nelson Leça

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  4. João Barbosa

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  5. António J Pereira

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  6. Helder Maiato

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  7. Claudio E Sunkel

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    For correspondence
    cesunkel@ibmc.up.pt
    Competing interests
    The authors declare that no competing interests exist.
  8. Carlos Conde

    i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
    For correspondence
    cconde@ibmc.up.pt
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4177-8519

Funding

FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 (Norte-01-0145-FEDER-000029)

  • Margarida Moura
  • Claudio E Sunkel
  • Carlos Conde

Fundação para a Ciência e a Tecnologia (PTDC7BEX-BCM/1921/2014-PR041602)

  • Claudio E Sunkel

Fundação para a Ciência e a Tecnologia (PEst-C/SAU/LA0002/2013-Incentivo2014-BGCT)

  • Claudio E Sunkel

Fundação para a Ciência e a Tecnologia (FCT Investigator grant IF/01755/2014)

  • Carlos Conde

Fundação para a Ciência e a Tecnologia (GABBA PhD Program grant PD/BD/105746/2014)

  • Mariana Osswald

Fundação para a Ciência e a Tecnologia (FCT PhD grant SFRH/BD/87871/2012)

  • João Barbosa

European Research Council (PRECISE)

  • Helder Maiato

European Research Council (CODECHECK)

  • Helder Maiato

FLAD Life Science

  • Helder Maiato

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany

Publication history

  1. Received: January 23, 2017
  2. Accepted: April 29, 2017
  3. Accepted Manuscript published: May 2, 2017 (version 1)
  4. Accepted Manuscript updated: May 4, 2017 (version 2)
  5. Version of Record published: May 16, 2017 (version 3)

Copyright

© 2017, Moura et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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