Suppressor Analysis Uncovers That MAPs and Microtubule Dynamics Balance with the Cut7/ Kinesin-5 Motor for Mitotic Spindle Assembly in Schizosaccharomyces pombe
G3:Genes, Genomes, Genetics Volume 9 Issue 1
Page 269-280
published_at 2019-01-01
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| File | |
| Title ( eng ) |
Suppressor Analysis Uncovers That MAPs and Microtubule Dynamics Balance with the Cut7/ Kinesin-5 Motor for Mitotic Spindle Assembly in Schizosaccharomyces pombe
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| Creator |
Yamada Yusuke
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| Source Title |
G3:Genes, Genomes, Genetics
G3:Genes, Genomes, GeneticsG3
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| Volume | 9 |
| Issue | 1 |
| Start Page | 269 |
| End Page | 280 |
| Abstract |
The Kinesin-5 motor Cut7 in Schizosaccharomyces pombe plays essential roles in spindle pole separation, leading to the assembly of bipolar spindle. In many organisms, simultaneous inactivation of Kinesin-14s neutralizes Kinesin-5 deficiency. To uncover the molecular network that counteracts Kinesin-5, we have conducted a genetic screening for suppressors that rescue the cut7-22 temperature sensitive mutation, and identified 10 loci. Next generation sequencing analysis reveals that causative mutations are mapped in genes encoding a-, b-tubulins and the microtubule plus-end tracking protein Mal3/EB1, in addition to the components of the Pkl1/Kinesin-14 complex. Moreover, the deletion of various genes required for microtubule nucleation/polymerization also suppresses the cut7 mutant. Intriguingly, Klp2/ Kinesin-14 levels on the spindles are significantly increased in cut7 mutants, whereas these increases are negated by suppressors, which may explain the suppression by these mutations/deletions. Consistent with this notion, mild overproduction of Klp2 in these double mutant cells confers temperature sensitivity. Surprisingly, treatment with a microtubule-destabilizing drug not only suppresses cut7 temperature sensitivity but also rescues the lethality resulting from the deletion of cut7, though a single klp2 deletion per se cannot compensate for the loss of Cut7. We propose that microtubule assembly and/or dynamics antagonize Cut7 functions, and that the orchestration between these two factors is crucial for bipolar spindle assembly.
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| Keywords |
fission yeast
kinesin
microtubule dynamics
mitotic spindle
suppressor
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| Descriptions |
This work was supported by the Japan Society for the Promotion of Science (JSPS) [KAKENHI Scientific Research (A) (16H02503 to T.T.), a Challenging Exploratory Research grant (16K14672 to T.T.), Scientific Research (C) (16K07694 to M.Y.)], the Naito Foundation (T.T.) and the Uehara Memorial Foundation (T.T). M.Y. and T.T. designed research.M.Y. and Y.Y. performed experiments and analyzed the data.
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| Language |
eng
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| Resource Type | journal article |
| Publisher |
Genetics Society of America
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| Date of Issued | 2019-01-01 |
| Rights |
Copyright © 2019 Yukawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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| Publish Type | Version of Record |
| Access Rights | open access |
| Source Identifier |
[ISSN] 2160-1836
[DOI] 10.1534/g3.118.200896
[DOI] https://doi.org/10.1534/g3.118.200896
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