Kinetochore-bound Mps1 regulates kinetochore–microtubule attachments via Ndc80 phosphorylation
Open Access
- 14 October 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 220 (12)
- https://doi.org/10.1083/jcb.202106130
Abstract
Dividing cells detect and correct erroneous kinetochore–microtubule attachments during mitosis, thereby avoiding chromosome missegregation. The Aurora B kinase phosphorylates microtubule-binding elements specifically at incorrectly attached kinetochores, promoting their release and providing another chance for proper attachments to form. However, growing evidence suggests that the Mps1 kinase is also required for error correction. Here we directly examine how Mps1 activity affects kinetochore–microtubule attachments using a reconstitution-based approach that allows us to separate its effects from Aurora B activity. When endogenous Mps1 that copurifies with kinetochores is activated in vitro, it weakens their attachments to microtubules via phosphorylation of Ndc80, a major microtubule-binding protein. This phosphorylation contributes to error correction because phospho-deficient Ndc80 mutants exhibit genetic interactions and segregation defects when combined with mutants in other error correction pathways. In addition, Mps1 phosphorylation of Ndc80 is stimulated on kinetochores lacking tension. These data suggest that Mps1 provides an additional mechanism for correcting erroneous kinetochore–microtubule attachments, complementing the well-known activity of Aurora B.Keywords
Funding Information
- National Science Foundation (DGE-1256082)
- Packard (2006-30521)
- National Institutes of Health (R01GM079373, P01GM105537, R35GM134842, R01GM064386)
- Fred Hutchinson
- University of Washington (P30 CA015704)
- Howard Hughes Medical Institute
This publication has 76 references indexed in Scilit:
- Phosphodependent Recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 Kinase Maintains the Spindle CheckpointCurrent Biology, 2012
- KNL1/Spc105 Recruits PP1 to Silence the Spindle Assembly CheckpointCurrent Biology, 2011
- Aurora Kinases and Protein Phosphatase 1 Mediate Chromosome Congression through Regulation of CENP-ECell, 2010
- Kinetochore Attachments Require an Interaction between Unstructured Tails on Microtubules and Ndc80Hec1Current Biology, 2008
- Kinetochore-Microtubule Attachment Relies on the Disordered N-Terminal Tail Domain of Hec1Current Biology, 2008
- Implications for Kinetochore-Microtubule Attachment from the Structure of an Engineered Ndc80 ComplexCell, 2008
- Mps1 Kinase Promotes Sister-Kinetochore Bi-orientation by a Tension-Dependent MechanismCurrent Biology, 2007
- Kinetochore Microtubule Dynamics and Attachment Stability Are Regulated by Hec1Cell, 2006
- The Conserved KMN Network Constitutes the Core Microtubule-Binding Site of the KinetochoreCell, 2006
- Mps1 Phosphorylation of Dam1 Couples Kinetochores to Microtubule Plus Ends at MetaphaseCurrent Biology, 2006