Mps1 regulates kinetochore-microtubule attachment stability via the Ska complex to ensure error-free chromosome segregation
UID: 11088
- Description
- Spindle assembly checkpoint (SAC) regulators such as the Mps1 kinase not only delay anaphase onset, but also correct improper chromosome-spindle linkages that would otherwise lead to missegregation and aneuploidy. However, the substrates and mechanisms involved in this pathway of error correction remain poorly understood. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K-fibers) epistatically to Aurora B, the other major error-correcting kinase. Through chemical genetics and quantitative proteomics, we identify both known and novel sites of Mps1- regulated phosphorylation at the outer kinetochore. Modification of these substrates was sensitive to microtubule tension and counterbalanced by the PP2A-B56 phosphatase, a positive regulator of chromosome-spindle interactions. Consistently, Mps1 inhibition rescued K-fiber stability after depleting PP2A-B56. We also identify the hinge region of the W-shaped Ska complex as a key effector of Mps1 at the kinetochore-microtubule interface, as mutations that mimic constitutive phosphorylation strongly destabilized K-fibers in vivo and inhibited the Ska complex’s conversion from lattice diffusion to end-coupled microtubule binding in vitro. Together these results provide new insights into how Mps1 modulates the microtubule-binding properties of the kinetochore to promote the selective stabilization of bipolar attachments and error-free chromosome segregation.
-
Access via PRIDE
Accession #: PXD006135 - Access Restrictions
-
Free to All
- Access Instructions
- All public datasets available in PRIDE Archive in the repository can be accessed via the website by FTP link, Web Service (for programmatic access), and the PRIDE Inspector stand-alone tool.
- Associated Publications
- Equipment Used
- Software Used
- Dataset Format(s)
- RAW
- Dataset Size
- 38.4 GB
Do you have or know of a dataset that should be added to the catalog? Let us know!