Protein phosphatase 1 inactivates Mps1 to ensure efficient spindle assembly checkpoint silencing
- i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
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.
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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.
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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Protein phosphatase 1 inactivates Mps1 to ensure efficient spindle assembly checkpoint silencing
eLife 6:e25366.
https://doi.org/10.7554/eLife.25366
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