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Unifying the mechanism of mitotic exit control in a spatiotemporal logical model
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Unifying the mechanism of mitotic exit control in a spatiotemporal logical model
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Journal Article
Unifying the mechanism of mitotic exit control in a spatiotemporal logical model
2020
Overview
The transition from mitosis into the first gap phase of the cell cycle in budding yeast is controlled by the Mitotic Exit Network (MEN). The network interprets spatiotemporal cues about the progression of mitosis and ensures that release of Cdc14 phosphatase occurs only after completion of key mitotic events. The MEN has been studied intensively; however, a unified understanding of how localisation and protein activity function together as a system is lacking. In this paper, we present a compartmental, logical model of the MEN that is capable of representing spatial aspects of regulation in parallel to control of enzymatic activity. We show that our model is capable of correctly predicting the phenotype of the majority of mutants we tested, including mutants that cause proteins to mislocalise. We use a continuous time implementation of the model to demonstrate that Cdc14 Early Anaphase Release (FEAR) ensures robust timing of anaphase, and we verify our findings in living cells. Furthermore, we show that our model can represent measured cell–cell variation in Spindle Position Checkpoint (SPoC) mutants. This work suggests a general approach to incorporate spatial effects into logical models. We anticipate that the model itself will be an important resource to experimental researchers, providing a rigorous platform to test hypotheses about regulation of mitotic exit.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Boolean
/ Cell Cycle Proteins - metabolism
/ Cell Cycle Proteins - physiology
/ Cell Nucleus Division - physiology
/ Cyclins
/ Kinases
/ M Phase Cell Cycle Checkpoints - genetics
/ M Phase Cell Cycle Checkpoints - physiology
/ Mitosis
/ Nodes
/ Protein Tyrosine Phosphatases - genetics
/ Protein Tyrosine Phosphatases - metabolism
/ Protein Tyrosine Phosphatases - physiology
/ Proteins
/ Research and Analysis Methods
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - metabolism
/ Saccharomyces cerevisiae Proteins - physiology
/ Saccharomycetales - genetics
/ Saccharomycetales - metabolism
/ Spindle Apparatus - physiology
/ Yeast
