Two XMAP215/TOG Microtubule Polymerases, Alp14 and Dis1, Play Non-Exchangeable, Distinct Roles in Microtubule Organisation in Fission Yeast

International Journal of Molecular Sciences Volume 20 Issue 20 Page 5108- published_at 2019-10-15
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Title ( eng )
Two XMAP215/TOG Microtubule Polymerases, Alp14 and Dis1, Play Non-Exchangeable, Distinct Roles in Microtubule Organisation in Fission Yeast
Creator
Kawakami Tomoki
Pinder Corinne
Source Title
International Journal of Molecular Sciences
Volume 20
Issue 20
Start Page 5108
Abstract
Proper bipolar spindle assembly underlies accurate chromosome segregation. A cohort of microtubule-associated proteins orchestrates spindle microtubule formation in a spatiotemporally coordinated manner. Among them, the conserved XMAP215/TOG family of microtubule polymerase plays a central role in spindle assembly. In fission yeast, two XMAP215/TOGmembers, Alp14 and Dis1, share essential roles in cell viability; however how these two proteins functionally collaborate remains undetermined. Here we show the functional interplay and specification of Alp14 and Dis1. Creation of new mutant alleles of alp14, which display temperature sensitivity in the absence of Dis1, enabled us to conduct detailed analyses of a double mutant. We have found that simultaneous inactivation of Alp14 and Dis1 results in early mitotic arrest with very short, fragile spindles. Intriguingly, these cells often undergo spindle collapse, leading to a lethal “cut” phenotype. By implementing an artificial targeting system, we have shown that Alp14 and Dis1 are not functionally exchangeable and as such are not merely redundant paralogues. Interestingly, while Alp14 promotes microtubule nucleation, Dis1 does not. Our results uncover that the intrinsic specification, not the spatial regulation, between Alp14 and Dis1 underlies the collaborative actions of these two XMAP215/TOG members in mitotic progression, spindle integrity and genome stability.
Keywords
fission yeast
microtubule polymerase
XMAP215/TOG
mitotic spindle
spindle pole body
kinetochore
Descriptions
This work was supported by the Japan Society for the Promotion of Science (JSPS) (KAKENHI Scientific Research (A) 16H02503 and the Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers (S2902) to T.T. and Scientific Research (C) 19K05813 to M.Y.).
Language
eng
Resource Type journal article
Publisher
MDPI
Date of Issued 2019-10-15
Rights
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Publish Type Version of Record
Access Rights open access
Source Identifier
[ISSN] 1661-6596
[ISSN] 1422-0067
[DOI] 10.3390/ijms20205108
[DOI] https://doi.org/10.3390/ijms20205108