Dynamics of SIN Asymmetry Establishment

Archana Bajpai, Anna Feoktistova, Jun Song Chen, Dannel McCollum, Masamitsu Sato, Rafael E. Carazo-Salas, Kathleen L. Gould, Attila Csikász-Nagy

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Article numbere1003147
    JournalPLoS Computational Biology
    Volume9
    Issue number7
    DOIs
    Publication statusPublished - 2013 Jul

    Fingerprint

    Phosphorylation
    Asymmetry
    asymmetry
    phosphorylation
    inhibitor
    Spindle Pole Bodies
    Cells
    spindle pole body
    scaffolding proteins
    Anaphase
    Molecular Models
    prediction
    cyclin-dependent kinase
    Cyclin-Dependent Kinases
    Schizosaccharomyces
    Schizosaccharomyces pombe
    anaphase
    Scaffolds (biology)
    Metaphase
    metaphase

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience
    • Ecology
    • Molecular Biology
    • Genetics
    • Ecology, Evolution, Behavior and Systematics
    • Modelling and Simulation
    • Computational Theory and Mathematics

    Cite this

    Bajpai, A., Feoktistova, A., Chen, J. S., McCollum, D., Sato, M., Carazo-Salas, R. E., ... Csikász-Nagy, A. (2013). Dynamics of SIN Asymmetry Establishment. PLoS Computational Biology, 9(7), [e1003147]. https://doi.org/10.1371/journal.pcbi.1003147

    Dynamics of SIN Asymmetry Establishment. / Bajpai, Archana; Feoktistova, Anna; Chen, Jun Song; McCollum, Dannel; Sato, Masamitsu; Carazo-Salas, Rafael E.; Gould, Kathleen L.; Csikász-Nagy, Attila.

    In: PLoS Computational Biology, Vol. 9, No. 7, e1003147, 07.2013.

    Research output: Contribution to journalArticle

    Bajpai, A, Feoktistova, A, Chen, JS, McCollum, D, Sato, M, Carazo-Salas, RE, Gould, KL & Csikász-Nagy, A 2013, 'Dynamics of SIN Asymmetry Establishment', PLoS Computational Biology, vol. 9, no. 7, e1003147. https://doi.org/10.1371/journal.pcbi.1003147
    Bajpai A, Feoktistova A, Chen JS, McCollum D, Sato M, Carazo-Salas RE et al. Dynamics of SIN Asymmetry Establishment. PLoS Computational Biology. 2013 Jul;9(7). e1003147. https://doi.org/10.1371/journal.pcbi.1003147
    Bajpai, Archana ; Feoktistova, Anna ; Chen, Jun Song ; McCollum, Dannel ; Sato, Masamitsu ; Carazo-Salas, Rafael E. ; Gould, Kathleen L. ; Csikász-Nagy, Attila. / Dynamics of SIN Asymmetry Establishment. In: PLoS Computational Biology. 2013 ; Vol. 9, No. 7.
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