Dynamics of SIN asymmetry establishment.

Timing of cell division is coordinated by the Septation Initiation Network (SIN) in fission yeast. SIN activation is initiated at the two spindle pole bodies (SPB) of the cell in metaphase, but only one of these SPBs contains an active SIN in anaphase, while SIN is inactivated in the other by the Cd...

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Autores principales:	Archana Bajpai, Anna Feoktistova, Jun-Song Chen, Dannel McCollum, Masamitsu Sato, Rafael E Carazo-Salas, Kathleen L Gould, Attila Csikász-Nagy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/629c65f6069d401386dd6545a9c7f988
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id	oai:doaj.org-article:629c65f6069d401386dd6545a9c7f988
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spelling	oai:doaj.org-article:629c65f6069d401386dd6545a9c7f9882021-11-18T05:52:00ZDynamics of SIN asymmetry establishment.1553-734X1553-735810.1371/journal.pcbi.1003147https://doaj.org/article/629c65f6069d401386dd6545a9c7f9882013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874188/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Timing of cell division is coordinated by the Septation Initiation Network (SIN) in fission yeast. SIN activation is initiated at the two spindle pole bodies (SPB) of the cell in metaphase, but only one of these SPBs contains an active SIN in anaphase, while SIN is inactivated in the other by the Cdc16-Byr4 GAP complex. Most of the factors that are needed for such asymmetry establishment have been already characterized, but we lack the molecular details that drive such quick asymmetric distribution of molecules at the two SPBs. Here we investigate the problem by computational modeling and, after establishing a minimal system with two antagonists that can drive reliable asymmetry establishment, we incorporate the current knowledge on the basic SIN regulators into an extended model with molecular details of the key regulators. The model can capture several peculiar earlier experimental findings and also predicts the behavior of double and triple SIN mutants. We experimentally tested one prediction, that phosphorylation of the scaffold protein Cdc11 by a SIN kinase and the core cell cycle regulatory Cyclin dependent kinase (Cdk) can compensate for mutations in the SIN inhibitor Cdc16 with different efficiencies. One aspect of the prediction failed, highlighting a potential hole in our current knowledge. Further experimental tests revealed that SIN induced Cdc11 phosphorylation might have two separate effects. We conclude that SIN asymmetry is established by the antagonistic interactions between SIN and its inhibitor Cdc16-Byr4, partially through the regulation of Cdc11 phosphorylation states.Archana BajpaiAnna FeoktistovaJun-Song ChenDannel McCollumMasamitsu SatoRafael E Carazo-SalasKathleen L GouldAttila Csikász-NagyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 7, p e1003147 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Archana Bajpai Anna Feoktistova Jun-Song Chen Dannel McCollum Masamitsu Sato Rafael E Carazo-Salas Kathleen L Gould Attila Csikász-Nagy Dynamics of SIN asymmetry establishment.
description	Timing of cell division is coordinated by the Septation Initiation Network (SIN) in fission yeast. SIN activation is initiated at the two spindle pole bodies (SPB) of the cell in metaphase, but only one of these SPBs contains an active SIN in anaphase, while SIN is inactivated in the other by the Cdc16-Byr4 GAP complex. Most of the factors that are needed for such asymmetry establishment have been already characterized, but we lack the molecular details that drive such quick asymmetric distribution of molecules at the two SPBs. Here we investigate the problem by computational modeling and, after establishing a minimal system with two antagonists that can drive reliable asymmetry establishment, we incorporate the current knowledge on the basic SIN regulators into an extended model with molecular details of the key regulators. The model can capture several peculiar earlier experimental findings and also predicts the behavior of double and triple SIN mutants. We experimentally tested one prediction, that phosphorylation of the scaffold protein Cdc11 by a SIN kinase and the core cell cycle regulatory Cyclin dependent kinase (Cdk) can compensate for mutations in the SIN inhibitor Cdc16 with different efficiencies. One aspect of the prediction failed, highlighting a potential hole in our current knowledge. Further experimental tests revealed that SIN induced Cdc11 phosphorylation might have two separate effects. We conclude that SIN asymmetry is established by the antagonistic interactions between SIN and its inhibitor Cdc16-Byr4, partially through the regulation of Cdc11 phosphorylation states.
format	article
author	Archana Bajpai Anna Feoktistova Jun-Song Chen Dannel McCollum Masamitsu Sato Rafael E Carazo-Salas Kathleen L Gould Attila Csikász-Nagy
author_facet	Archana Bajpai Anna Feoktistova Jun-Song Chen Dannel McCollum Masamitsu Sato Rafael E Carazo-Salas Kathleen L Gould Attila Csikász-Nagy
author_sort	Archana Bajpai
title	Dynamics of SIN asymmetry establishment.
title_short	Dynamics of SIN asymmetry establishment.
title_full	Dynamics of SIN asymmetry establishment.
title_fullStr	Dynamics of SIN asymmetry establishment.
title_full_unstemmed	Dynamics of SIN asymmetry establishment.
title_sort	dynamics of sin asymmetry establishment.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/629c65f6069d401386dd6545a9c7f988
work_keys_str_mv	AT archanabajpai dynamicsofsinasymmetryestablishment AT annafeoktistova dynamicsofsinasymmetryestablishment AT junsongchen dynamicsofsinasymmetryestablishment AT dannelmccollum dynamicsofsinasymmetryestablishment AT masamitsusato dynamicsofsinasymmetryestablishment AT rafaelecarazosalas dynamicsofsinasymmetryestablishment AT kathleenlgould dynamicsofsinasymmetryestablishment AT attilacsikasznagy dynamicsofsinasymmetryestablishment
_version_	1718424729320161280

Dynamics of SIN asymmetry establishment.

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