A mitotic SKAP isoform regulates spindle positioning at astral microtubule plus ends
Name
Kern-2016-A mitotic SKAP isofo.pdf
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2.93 MB
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Author(s)
Nicholls, Peter K.
Kern, David Matthew
Page, David C
Cheeseman, Iain M
Date Issued
May 2016
Journal
The Journal of Cell Biology
Publisher
Rockefeller University Press
Citation
Kern, David M. et al. “A Mitotic SKAP Isoform Regulates Spindle Positioning at Astral Microtubule plus Ends.” The Journal of Cell Biology 213.3 (2016): 315–328.
Version
Final published version
Abstract
The Astrin/SKAP complex plays important roles in mitotic chromosome alignment and centrosome integrity, but previous work found conflicting results for SKAP function. Here, we demonstrate that SKAP is expressed as two distinct isoforms in mammals: a longer, testis-specific isoform that was used for the previous studies in mitotic cells and a novel, shorter
mitotic isoform. Unlike the long isoform, short SKAP rescues SKAP depletion in mitosis and displays robust microtubule plus-end tracking, including localization to astral microtubules. Eliminating SKAP microtubule binding results in severe chromosome segregation defects. In contrast, SKAP mutants specifically defective for plus-end tracking facilitate proper
chromosome segregation but display spindle positioning defects. Cells lacking SKAP plus-end tracking have reduced Clasp1 localization at microtubule plus ends and display increased lateral microtubule contacts with the cell cortex, which we propose results in unbalanced dynein-dependent cortical pulling forces. Our work reveals an unappreciated role for the Astrin/SKAP complex as an astral microtubule mediator of mitotic spindle positioning.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1083/jcb.201510117
