Accurate mitosis requires kinetochores to make persistent, load-bearing attachments to dynamic microtubule tips, thereby coupling chromosome movements to tip growth and shortening. This tip-coupling behavior depends on the conserved Ndc80 complex and, in budding yeast, on the Dam1 complex, which bind each other directly via three distinct interacting regions. The functional relevance of these multiple interactions was mysterious. Here we show that interactions between two of these regions support the high rupture strengths that occur when applied force is rapidly increased and also support the stability of tip-coupling when force is held constant over longer durations. The contribution of either of these two regions to tip-coupling is reduced by phosphorylation by Aurora B kinase. The third interaction region makes no apparent contribution to rupture strength, but its phosphorylation by Aurora B kinase specifically decreases the long-term stability of tip-coupling. The specific reduction of long-term stability relative to short-term strength might have important implications for mitotic error correction.
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2 May 2022
Article|
March 30 2022
Three interacting regions of the Ndc80 and Dam1 complexes support microtubule tip-coupling under load
Rachel L. Flores,
Rachel L. Flores
1
Department of Biochemistry, University of Washington, Seattle, WA
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Zachary E. Peterson
,
Zachary E. Peterson
1
Department of Biochemistry, University of Washington, Seattle, WA
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Alex Zelter
,
Alex Zelter
1
Department of Biochemistry, University of Washington, Seattle, WA
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Michael Riffle
,
Michael Riffle
1
Department of Biochemistry, University of Washington, Seattle, WA
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Charles L. Asbury
,
2
Department of Physiology and Biophysics, University of Washington, Seattle, WA
Correspondence to Charles L. Asbury: casbury@uw.edu
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Trisha N. Davis
1
Department of Biochemistry, University of Washington, Seattle, WA
Trisha N. Davis: tdavis@uw.edu
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Rachel L. Flores
1
Department of Biochemistry, University of Washington, Seattle, WA
Zachary E. Peterson
1
Department of Biochemistry, University of Washington, Seattle, WA
Alex Zelter
1
Department of Biochemistry, University of Washington, Seattle, WA
Michael Riffle
1
Department of Biochemistry, University of Washington, Seattle, WA
2
Department of Physiology and Biophysics, University of Washington, Seattle, WA
1
Department of Biochemistry, University of Washington, Seattle, WA
Correspondence to Charles L. Asbury: casbury@uw.edu
Trisha N. Davis: tdavis@uw.edu
*
C.L. Asbury and T.N. Davis share last authorship.
Received:
July 02 2021
Revision Received:
December 20 2021
Accepted:
March 07 2022
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
National Science Foundation
Funder(s):
Washington’s Proteomics Resource
- Award Id(s): UWPR95794
Funder(s):
National Institutes of Health
- Award Id(s): R01GM040506,R35GM130293
Funder(s):
National Institutes of Health
- Award Id(s): R01GM079373,R35GM134842
© 2022 Flores et al.
2022
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2022) 221 (5): e202107016.
Article history
Received:
July 02 2021
Revision Received:
December 20 2021
Accepted:
March 07 2022
Citation
Rachel L. Flores, Zachary E. Peterson, Alex Zelter, Michael Riffle, Charles L. Asbury, Trisha N. Davis; Three interacting regions of the Ndc80 and Dam1 complexes support microtubule tip-coupling under load. J Cell Biol 2 May 2022; 221 (5): e202107016. doi: https://doi.org/10.1083/jcb.202107016
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