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The Astrin-SKAP Complex Reduces Friction at the Kinetochore-Microtubule Interface

View ORCID ProfileMiquel Rosas-Salvans, View ORCID ProfileRenaldo Sutanto, View ORCID ProfilePooja Suresh, View ORCID ProfileSophie Dumont
doi: https://doi.org/10.1101/2021.11.29.469773
Miquel Rosas-Salvans
1Dept of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA
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  • For correspondence: miquel.rosas377@gmail.com sophie.dumont@ucsf.edu
Renaldo Sutanto
1Dept of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA
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Pooja Suresh
1Dept of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA
2Biophysics Graduate Program, UCSF, San Francisco, CA
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Sophie Dumont
1Dept of Bioengineering & Therapeutic Sciences, UCSF, San Francisco, CA
2Biophysics Graduate Program, UCSF, San Francisco, CA
3Dept of Biochemistry & Biophysics, UCSF, San Francisco, CA
4Chan Zuckerberg Biohub, San Francisco, CA
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  • For correspondence: miquel.rosas377@gmail.com sophie.dumont@ucsf.edu
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ABSTRACT

The kinetochore links chromosomes to spindle microtubules to drive chromosome segregation at cell division. While we know nearly all mammalian kinetochore proteins, how these give rise to the strong yet dynamic microtubule attachments required for function remains poorly understood. Here, we focus on the Astrin-SKAP complex, which localizes to bioriented kinetochores and is essential for chromosome segregation, but whose mechanical role is unclear. Live imaging reveals that SKAP depletion dampens movement and decreases coordination of metaphase sister kinetochores, and increases tension between them. Using laser ablation to isolate kinetochores bound to polymerizing vs depolymerizing microtubules, we show that without SKAP kinetochores move slower on both polymerizing and depolymerizing microtubules, and that more force is needed to rescue microtubules to polymerize. Thus, in contrast to previously described kinetochore proteins that increase grip on microtubules under force, Astrin-SKAP reduces grip, increasing attachment dynamics and force responsiveness and reducing friction. Together, our findings suggest a model where the Astrin-SKAP complex effectively “lubricates” correct, bioriented attachments to help preserve them.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 30, 2021.
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The Astrin-SKAP Complex Reduces Friction at the Kinetochore-Microtubule Interface
Miquel Rosas-Salvans, Renaldo Sutanto, Pooja Suresh, Sophie Dumont
bioRxiv 2021.11.29.469773; doi: https://doi.org/10.1101/2021.11.29.469773
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The Astrin-SKAP Complex Reduces Friction at the Kinetochore-Microtubule Interface
Miquel Rosas-Salvans, Renaldo Sutanto, Pooja Suresh, Sophie Dumont
bioRxiv 2021.11.29.469773; doi: https://doi.org/10.1101/2021.11.29.469773

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