Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore

Kinetochores attach the replicated chromosomes to the mitotic spindle and orchestrate their transmission to the daughter cells. Kinetochore–spindle binding and chromosome segregation are mediated by the multi-copy KNL1 Spc105 , MIS12 Mtw1 and NDC80 Ndc80  complexes that form the so-called KMN networ...

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Published inNature cell biology Vol. 14; no. 6; pp. 614 - 624
Main Authors Bock, Lucy J., Pagliuca, Cinzia, Kobayashi, Norihiko, Grove, Ryan A., Oku, Yusuke, Shrestha, Kriti, Alfieri, Claudio, Golfieri, Cristina, Oldani, Amanda, Dal Maschio, Marianna, Bermejo, Rodrigo, Hazbun, Tony R., Tanaka, Tomoyuki U., De Wulf, Peter
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.06.2012
Nature Publishing Group
Subjects
631/80/641/1966
631/80/641/2002
Anaphase
Biomedical and Life Sciences
Cancer Research
Cell Biology
Cell cycle
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Chromosomes
Chromosomes, Fungal - metabolism
Developmental Biology
Genetic aspects
Kinases
Kinetochores
Kinetochores - metabolism
Life Sciences
Microtubule-Associated Proteins - genetics
Microtubule-Associated Proteins - metabolism
Oncology
Phosphorylation
Physiological aspects
Protein Binding
Protein Serine-Threonine Kinases - genetics
Protein Serine-Threonine Kinases - metabolism
Proteins
Saccharomyces cerevisiae
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Spindle Apparatus - metabolism
Stem Cells
Yeast
Yeast fungi
Yeasts
United States
United Kingdom
Italy
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Summary:Kinetochores attach the replicated chromosomes to the mitotic spindle and orchestrate their transmission to the daughter cells. Kinetochore–spindle binding and chromosome segregation are mediated by the multi-copy KNL1 Spc105 , MIS12 Mtw1 and NDC80 Ndc80  complexes that form the so-called KMN network. KMN–spindle attachment is regulated by the Aurora B Ipl1 and MPS1 Mps1  kinases. It is unclear whether other mechanisms exist that support KMN activity during the cell cycle. Using budding yeast, we show that kinetochore protein Cnn1 localizes to the base of the Ndc80 complex and promotes a functionally competent configuration of the KMN network. Cnn1 regulates KMN activity in a spatiotemporal manner by inhibiting the interaction between its complexes. Cnn1 activity peaks in anaphase and is driven by the Cdc28, Mps1 and Ipl1 kinases. The kinetochore is a multiprotein complex that tethers chromosomes to the mitotic spindle for accurate chromosome segregation. De Wulf and colleagues now show in budding yeast that the protein Cnn1 functions at the kinetochore and is recruited to the inner kinetochore, in a manner dependent on its phosphorylation mediated by the Cdc28, Mps1 and Ipl1 kinases.
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AUTHOR CONTRIBUTIONS L.J.B. and C.P. performed all the genetic, molecular biological, biochemical and cell biological experiments. N.K. performed the time-lapse CEN-reactivation and Cnn1–3GFP imaging experiments, R.A.G. performed the Y2H screens, Y.O. performed the in vitro kinase experiments, K.S. performed the in vitro Cnn1–KMN binding experiments, C.A. helped with the genetic interaction screens and the ChIP–chip experiment, C.G. and M.D.M. performed the cell-cycle experiments, PhosTag western hybridization and Cnn1–Cnn1 co-immunoprecipitation experiments. A.O. performed the FRAP experiments and helped with the quantification of Cnn1–3GFP and Ndc80–3GFP at kinetochores, R.B. helped with the ChIP–chip experiment and converted the microarray data into graphic format, T.R.H. supervised the Y2H screens and the in vitro Cnn1–KMN binding experiments. T.U.T. supervised the live-cell imaging experiments. P.D.W. supervised the project, helped with yeast imaging and wrote the paper.
These authors contributed equally to this work.
ISSN:1465-7392
1476-4679
1476-4679
DOI:10.1038/ncb2495