Cdc5-Dependent Asymmetric Localization of Bfa1 Fine-Tunes Timely MitoticExit

Collection with item attached
2012
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/475755.do
DOI
10.1371/journal.pgen.1002450
Title
Cdc5-Dependent Asymmetric Localization of Bfa1 Fine-Tunes Timely MitoticExit
Description
This work was supported by a grant from the 21C Frontier MicrobialGenomics and Application Center Program, the Ministry of Education,Science, and Technology of the Republic of Korea (11-2008-10-005-00). GLwas partly supported by a fellowship from the Brain Korea 21 (BK21)Program. The funders had no role in study design, data collection andanalysis, decision to publish, or preparation of the manuscript.
abstract
In budding yeast, the major regulator of the mitotic exit network (MEN) is Tem1, a GTPase, which is inhibited by the GTPase-activating protein (GAP), Bfa1/Bub2. Asymmetric Bfa1 localization to the bud-directed spindle pole body (SPB) during metaphase also controls mitotic exit, but the molecular mechanism and function of this localization are not well understood, particularly in unperturbed cells. We identified four novel Cdc5 target residues within the Bfa1 C-terminus: S-452, S-453, S-454, and S-559. A Bfa1 mutant in which all of these residues had been changed to alanine (Bfa1(4A)) persisted on both SPBs at anaphase and was hypo-phosphorylated, despite retaining its GAP activity for Tem1. A Bfa1 phosphomimetic mutant in which all of these residues were switched to aspartate (Bfa1(4D)) always localized asymmetrically to the SPB. These observations demonstrate that asymmetric localization of Bfa1 is tightly linked to its Cdc5-dependent phosphorylation, but not to its GAP activity. Consistent with this, in kinase-defective cdc5-2 cells Bfa1 was not phosphorylated and localized to both SPBs, whereas Bfa1(4D) was asymmetrically localized. BFA1(4A) cells progressed through anaphase normally but displayed delayed mitotic exit in unperturbed cell cycles, while BFA1(4D) cells underwent mitotic exit with the same kinetics as wild-type cells. We suggest that Cdc5 induces the asymmetric distribution of Bfa1 to the bud-directed SPB independently of Bfa1 GAP activity at anaphase and that Bfa1 asymmetry fine-tunes the timing of MEN activation in unperturbed cell cycles.
provenance
Made available in Cube on 2018-09-28T11:21:21Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Junwon
Luo, Guangming
Bahk, Young Yil
Song, Kiwon
accessioned
2018-09-28T11:21:21Z
available
2018-09-28T11:21:21Z
issued
2012
citation
PLOS GENETICS(8): 1
issn
1553-7390
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/475755.do
Funder
교육과학기술부
Funding Program
2단계연구중심대학육성(0.5)
Project ID
1345196750
Jurisdiction
Rep.of Korea
Project Name
Yonsei Biomolecule Research Initiative
rights
openAccess
type
article


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