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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874188/pdf/?tool=EBI |
| _version_ | 1818347919484387328 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T17:41:49Z |
| format | Article |
| id | doaj.art-629c65f6069d401386dd6545a9c7f988 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-13T17:41:49Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-629c65f6069d401386dd6545a9c7f9882022-12-21T23:36:43ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582013-01-0197e100314710.1371/journal.pcbi.1003147Dynamics of SIN asymmetry establishment.Archana BajpaiAnna FeoktistovaJun-Song ChenDannel McCollumMasamitsu SatoRafael E Carazo-SalasKathleen L GouldAttila Csikász-NagyTiming 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874188/pdf/?tool=EBI |
| spellingShingle | 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. PLoS Computational Biology |
| title | 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_short | Dynamics of SIN asymmetry establishment. |
| title_sort | dynamics of sin asymmetry establishment |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874188/pdf/?tool=EBI |
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