Mps1 regulates kinetochore-microtubule attachment stability via the Ska complex to ensure error-free chromosome segregation Journal Article
| Authors: | Maciejowski, J.; Drechsler, H.; Grundner-Culemann, K.; Ballister, E. R.; Rodriguez-Rodriguez, J. A.; Rodriguez-Bravo, V.; Jones, M. J. K.; Foley, E.; Lampson, M. A.; Daub, H.; McAinsh, A. D.; Jallepalli, P. V. |
| Article Title: | Mps1 regulates kinetochore-microtubule attachment stability via the Ska complex to ensure error-free chromosome segregation |
| Abstract: | The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1’s error correction-relevant substrates are unknown. 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 quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore. Substrate modification was microtubule sensitive and opposed by PP2A-B56 phosphatases that stabilize chromosome-spindle attachment. Consistently, Mps1 inhibition rescued K-fiber stability after depleting PP2A-B56. We also identify the Ska complex as a key effector of Mps1 at the kinetochore-microtubule interface, as mutations that mimic constitutive phosphorylation destabilized K fibers in vivo and reduced the efficiency of the Ska complex's conversion from lattice diffusion to end-coupled microtubule binding in vitro. Our results reveal how Mps1 dynamically modifies kinetochores to correct improper attachments and ensure faithful chromosome segregation. © 2017 Elsevier Inc. |
| Keywords: | controlled study; protein phosphorylation; unclassified drug; mutation; mitosis; mass spectrometry; diffusion; protein binding; protein stability; in vitro study; phosphorylation; proteomics; quantitative analysis; microtubule; cell adhesion; protein kinase; phosphotransferase; metaphase; chromosome segregation; aurora b kinase; phosphoprotein phosphatase 2a; peptides and proteins; mitotic spindle; kinetochore; priority journal; article; kinetochore microtubule; mps1; ska complex; ska1; mps1 protein |
| Journal Title: | Developmental Cell |
| Volume: | 41 |
| Issue: | 2 |
| ISSN: | 1534-5807 |
| Publisher: | Cell Press |
| Date Published: | 2017-04-24 |
| Start Page: | 143 |
| End Page: | 156.e6 |
| Language: | English |
| DOI: | 10.1016/j.devcel.2017.03.025 |
| PROVIDER: | scopus |
| PUBMED: | 28441529 |
| PMCID: | PMC5477644 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 June 2017 -- Source: Scopus |
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