The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast

Cell Cycle Volume 15 Issue 5 Page 740-747 published_at 2016-03-30
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Title ( eng )
The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast
Creator
Chmielewska Aldona Ewa
Tang Ngang Heok
Source Title
Cell Cycle
Volume 15
Issue 5
Start Page 740
End Page 747
Abstract
The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1.
Keywords
fission yeast
kinetochore
Mph1/MPS1
Ndc80
spindle assembly checkpoint
Descriptions
This work was supported by by Cancer Research UK—by Cancer Research UK and the Francis Crick Institute.
Language
eng
Resource Type journal article
Publisher
Taylor & Francis Group, LLC
Date of Issued 2016-03-30
Rights
© The Francis Crick Institute. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
Publish Type Version of Record
Access Rights open access
Source Identifier
[ISSN] 1538-4101
[ISSN] 1551-4005
[DOI] 10.1080/15384101.2016.1148842
[PMID] 26900649
[DOI] https://doi.org/10.1080/15384101.2016.1148842