Bud-Localization of CLB2 mRNA Can Constitute a Growth Rate Dependent Daughter Sizer
| Autor: | Edda Klipp, Thomas W. Spiesser, Marcus Krantz, Clemens Kühn |
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| Rok vydání: | 2014 |
| Předmět: |
Cell cycle checkpoint
Saccharomyces cerevisiae Proteins Saccharomyces cerevisiae Cyclin B Cell Enlargement Models Biological Cellular and Molecular Neuroscience Genetics Computer Simulation RNA Messenger lcsh:QH301-705.5 Molecular Biology Ecology Evolution Behavior and Systematics Cyclin Ecology biology Cell growth Translation (biology) Cell Cycle Checkpoints Cell cycle biology.organism_classification Cell biology lcsh:Biology (General) Computational Theory and Mathematics Modeling and Simulation biology.protein Subcellular Fractions Research Article |
| Zdroj: | PLoS Computational Biology PLoS Computational Biology, Vol 11, Iss 4, p e1004223 (2015) |
| ISSN: | 1553-7358 |
| Popis: | Maintenance of cellular size is a fundamental systems level process that requires balancing of cell growth with proliferation. This is achieved via the cell division cycle, which is driven by the sequential accumulation and destruction of cyclins. The regulatory network around these cyclins, particularly in G1, has been interpreted as a size control network in budding yeast, and cell size as being decisive for the START transition. However, it is not clear why disruptions in the G1 network may lead to altered size rather than loss of size control, or why the S-G2-M duration also depends on nutrients. With a mathematical population model comprised of individually growing cells, we show that cyclin translation would suffice to explain the observed growth rate dependence of cell volume at START. Moreover, we assess the impact of the observed bud-localisation of the G2 cyclin CLB2 mRNA, and find that localised cyclin translation could provide an efficient mechanism for measuring the biosynthetic capacity in specific compartments: The mother in G1, and the growing bud in G2. Hence, iteration of the same principle can ensure that the mother cell is strong enough to grow a bud, and that the bud is strong enough for independent life. Cell sizes emerge in the model, which predicts that a single CDK-cyclin pair per growth phase suffices for size control in budding yeast, despite the necessity of the cell cycle network around the cyclins to integrate other cues. Size control seems to be exerted twice, where the G2/M control affects bud size through bud-localized translation of CLB2 mRNA, explaining the dependence of the S-G2-M duration on nutrients. Taken together, our findings suggest that cell size is an emergent rather than a regulatory property of the network linking growth and proliferation. Author Summary The size between different organisms ranges considerably, yet, the size of the individuals and even the same types of cells within the individuals are remarkably constant. Cell size emerges from the balance between how fast the cell grows and the frequency with which it divides. This system level coordination of growth and division is universal across species and is required to ensure faithful duplication and genetically intact offspring. We have devised a computational model for the interplay of growth and division in the premier model organism, Baker’s yeast, to test the fundamental architecture of this coupling and to assess the role that cell size itself can play in it. In contrast to traditional theories that assume a yet-to-be-determined cell size sensor, our model relies on a single mechanism, effectively measuring the cell’s translational capacity, applied twice at different stages of the cell’s life-cycle to explain this coupling. In our model, a growth condition specific cell size emerges, as has been found in experiments. Our analysis shows how the nature of the two linked properties growth and proliferation can shape eukaryotic cells and explain cell size as an emergent rather than regulatory property of this process. |
| Databáze: | OpenAIRE |
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