scholarly journals Size-Dependent Expression of the Mitotic Activator Cdc25 as a Mechanism of Size Control in Fission Yeast

2016 ◽  
Author(s):  
Daniel Keifenheim ◽  
Xi-Ming Sun ◽  
Edridge D'Souza ◽  
Makoto J. Ohira ◽  
Mira Magner ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Cell Size ◽  
Budding Yeast ◽  
Size Control ◽  
Population Level ◽  
Threshold Concentration ◽  
Fixed Amount ◽  
Size Dependent ◽  
Population Average ◽  
The Subject

SummaryProper cell size is essential for cellular function (Hall et al., 2004). Nonetheless, despite more than 100 years of work on the subject, the mechanisms that maintain cell size homeostasis are largely mysterious (Marshall et al., 2012). Cells in growing populations maintain cell size within a narrow range by coordinating growth and division. Bacterial and eukaryotic cells both demonstrate homeostatic size control, which maintains population-level variation in cell size within a certain range, and returns the population average to that range if it is perturbed (Marshall et al., 2012; Turner et al., 2012; Amodeo and Skotheim, 2015). Recent work has proposed two different strategies for size control: budding yeast has been proposed to use an inhibitor-dilution strategy to regulate size at the G1/S transition (Schmoller et al., 2015), while bacteria appear to use an adder strategy, in which a fixed amount of growth each generation causes cell size to converge on a stable average, a mechanism also suggested for budding yeast (Campos et al., 2014; Jun and Taheri-Araghi, 2015; Taheri-Araghi et al., 2015; Tanouchi et al., 2015; Soifer et al., 2016). Here we present evidence that cell size in the fission yeast Schizosaccharomyces pombe is regulated by a third strategy: the size dependent expression of the mitotic activator Cdc25. The cdc25 transcript levels are regulated such that smaller cells express less Cdc25 and larger cells express more Cdc25, creating an increasing concentration of Cdc25 as cell grow and providing a mechanism for cell to trigger cell division when they reach a threshold concentration of Cdc25. Since regulation of mitotic entry by Cdc25 is well conserved, this mechanism may provide a wide spread solution to the problem of size control in eukaryotes.

scholarly journals Cell size-dependent regulation of Wee1 localization by Cdr2 cortical nodes

2017 ◽  
Author(s):  
Corey A. H. Allard ◽  
Hannah E. Opalko ◽  
Ko-Wei Liu ◽  
Uche Medoh ◽  
James B. Moseley
Keyword(s):  
Cell Growth ◽  
Fission Yeast ◽  
Cell Size ◽  
Kinase Activity ◽  
Size Control ◽  
Small Cells ◽  
Mitotic Entry ◽  
Size Dependent ◽  
Biochemical Fractionation ◽  
Mitotic Inhibitor

AbstractCell size control requires mechanisms that link cell growth with Cdk1 activity. In fission yeast, the protein kinase Cdr2 forms cortical nodes that include the Cdk1 inhibitor Wee1, along with the Wee1-inhibitory kinase Cdr1. We investigated how nodes inhibit Wee1 during cell growth. Biochemical fractionation revealed that Cdr2 nodes were megadalton structures enriched for activated Cdr2, which increases in level during interphase growth. In live-cell TIRF movies, Cdr2 and Cdr1 remained constant at nodes over time, but Wee1 localized to nodes in short bursts. Recruitment of Wee1 to nodes required Cdr2 kinase activity and the noncatalytic N-terminus of Wee1. Bursts of Wee1 localization to nodes increased 20-fold as cells doubled in size throughout G2. Size-dependent signaling was due in part to the Cdr2 inhibitor Pom1, which suppressed Wee1 node bursts in small cells. Thus, increasing Cdr2 activity during cell growth promotes Wee1 localization to nodes, where inhibitory phosphorylation of Wee1 by Cdr1 and Cdr2 kinases promotes mitotic entry.SummaryCells turn off the mitotic inhibitor Wee1 to enter into mitosis. This study shows how cell growth progressively inhibits fission yeast Wee1 through dynamic bursts of localization to cortical node structures that contain Wee1 inhibitory kinases.

scholarly journals Daughter-Specific Transcription Factors Regulate Cell Size Control in Budding Yeast

PLoS Biology ◽  
2009 ◽  
Vol 7 (10) ◽  
pp. e1000221 ◽  
Author(s):  
Stefano Di Talia ◽  
Hongyin Wang ◽  
Jan M. Skotheim ◽  
Adam P. Rosebrock ◽  
Bruce Futcher ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Size ◽  
Budding Yeast ◽  
Size Control ◽  
Cell Size Control

scholarly journals Characterizing non-exponential growth and bimodal cell size distributions in Schizosaccharomyces pombe: an analytical approach

2021 ◽  
Author(s):  
Chen Jia ◽  
Abhyudai Singh ◽  
Ramon Grima
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Cell Size ◽  
Control Strategy ◽  
Size Control ◽  
Birth Size ◽  
Size Distributions ◽  
Cell Size Distribution ◽  
A Cell ◽  
Cell Size Control

Unlike many single-celled organisms, the growth of fission yeast cells within a cell cycle is not exponential. It is rather characterized by three distinct phases (elongation, septation and fission), each with a different growth rate. Experiments also show that the distribution of cell size in a lineage is often bimodal, unlike the unimodal distributions measured for the bacterium Escherichia coli. Here we construct a detailed stochastic model of cell size dynamics in fission yeast. The theory leads to analytic expressions for the cell size and the birth size distributions, and explains the origin of bimodality seen in experiments. In particular our theory shows that the left peak in the bimodal distribution is associated with cells in the elongation phase while the right peak is due to cells in the septation and fission phases. We show that the size control strategy, the variability in the added size during a cell cycle and the fraction of time spent in each of the three cell growth phases have a strong bearing on the shape of the cell size distribution. Furthermore we infer all the parameters of our model by matching the theoretical cell size and birth size distributions to those from experimental single cell time-course data for seven different growth conditions. Our method provides a much more accurate means of determining the cell size control strategy (timer, adder or sizer) than the standard method based on the slope of the best linear fit between the birth and division sizes. We also show that the variability in added size and the strength of cell size control of fission yeast depend weakly on the temperature but strongly on the culture medium.

scholarly journals Cell size–dependent regulation of Wee1 localization by Cdr2 cortical nodes

2018 ◽  
Vol 217 (5) ◽  
pp. 1589-1599 ◽  
Author(s):  
Corey A.H. Allard ◽  
Hannah E. Opalko ◽  
Ko-Wei Liu ◽  
Uche Medoh ◽  
James B. Moseley
Keyword(s):  
Cell Growth ◽  
Cell Size ◽  
Total Internal Reflection ◽  
Kinase Activity ◽  
Size Control ◽  
Small Cells ◽  
Mitotic Entry ◽  
Size Dependent ◽  
N Terminus ◽  
Biochemical Fractionation

Cell size control requires mechanisms that link cell growth with Cdk1 activity. In fission yeast, the protein kinase Cdr2 forms cortical nodes that include the Cdk1 inhibitor Wee1 along with the Wee1-inhibitory kinase Cdr1. We investigated how nodes inhibit Wee1 during cell growth. Biochemical fractionation revealed that Cdr2 nodes were megadalton structures enriched for activated Cdr2, which increases in level during interphase growth. In live-cell total internal reflection fluorescence microscopy videos, Cdr2 and Cdr1 remained constant at nodes over time, but Wee1 localized to nodes in short bursts. Recruitment of Wee1 to nodes required Cdr2 kinase activity and the noncatalytic N terminus of Wee1. Bursts of Wee1 localization to nodes increased 20-fold as cells doubled in size throughout G2. Size-dependent signaling was caused in part by the Cdr2 inhibitor Pom1, which suppressed Wee1 node bursts in small cells. Thus, increasing Cdr2 activity during cell growth promotes Wee1 localization to nodes, where inhibitory phosphorylation of Wee1 by Cdr1 and Cdr2 kinases promotes mitotic entry.

scholarly journals Reprogramming Cdr2-Dependent Geometry-Based Cell Size Control in Fission Yeast

2019 ◽  
Vol 29 (2) ◽  
pp. 350-358.e4 ◽  
Author(s):  
Giuseppe Facchetti ◽  
Benjamin Knapp ◽  
Ignacio Flor-Parra ◽  
Fred Chang ◽  
Martin Howard
Keyword(s):  
Fission Yeast ◽  
Cell Size ◽  
Size Control ◽  
Cell Size Control

scholarly journals Scaling gene expression for cell size control and senescence in Saccharomyces cerevisiae

2020 ◽  
Author(s):  
Yuping Chen ◽  
Bruce Futcher
Keyword(s):  
Gene Expression ◽  
Cell Size ◽  
Size Control ◽  
Gene Expression Program ◽  
Set Point ◽  
Size Dependent ◽  
Large Size ◽  
Mean Size ◽  
Almost All ◽  
Expression Program

Abstract Cells divide with appropriate frequency by coupling division to growth—that is, cells divide only when they have grown sufficiently large. This process is poorly understood, but has been studied using cell size mutants. In principle, mutations affecting cell size could affect the mean size (“set-point” mutants), or they could affect the variability of sizes (“homeostasis” mutants). In practice, almost all known size mutants affect set-point, with little effect on size homeostasis. One model for size-dependent division depends on a size-dependent gene expression program: Activators of cell division are over-expressed at larger and larger sizes, while inhibitors are under-expressed. At sufficiently large size, activators overcome inhibitors, and the cell divides. Amounts of activators and inhibitors determine the set-point, but the gene expression program (the rate at which expression changes with cell size) determines the breadth of the size distribution (homeostasis). In this model, set-point mutants identify cell cycle activators and inhibitors, while homeostasis mutants identify regulators that couple expression of activators and inhibitors to size. We consider recent results suggesting that increased cell size causes senescence, and suggest that at very large sizes, an excess of DNA binding proteins leads to size induced senescence.

scholarly journals Cell-size regulation in budding yeast does not depend on linear accumulation of Whi5

2020 ◽  
Vol 117 (25) ◽  
pp. 14243-14250 ◽  
Author(s):  
Felix Barber ◽  
Ariel Amir ◽  
Andrew W. Murray
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Cell Cycle Regulation ◽  
Budding Yeast ◽  
Size Control ◽  
Size Distributions ◽  
Wild Type ◽  
Gal1 Promoter ◽  
The Mean ◽  
Cycle Regulation

Cells must couple cell-cycle progress to their growth rate to restrict the spread of cell sizes present throughout a population. Linear, rather than exponential, accumulation of Whi5, was proposed to provide this coordination by causing a higher Whi5 concentration in cells born at a smaller size. We tested this model using the inducibleGAL1promoter to make the Whi5 concentration independent of cell size. At an expression level that equalizes the mean cell size with that of wild-type cells, the size distributions of cells with galactose-induced Whi5 expression and wild-type cells are indistinguishable. Fluorescence microscopy confirms that the endogenous andGAL1promoters produce different relationships between Whi5 concentration and cell volume without diminishing size control in the G1 phase. We also expressed Cln3 from the GAL1 promoter, finding that the spread in cell sizes for an asynchronous population is unaffected by this perturbation. Our findings indicate that size control in budding yeast does not fundamentally originate from the linear accumulation of Whi5, contradicting a previous claim and demonstrating the need for further models of cell-cycle regulation to explain how cell size controls passage through Start.

scholarly journals Increasing cell size remodels the proteome and promotes senescence

2021 ◽  
Author(s):  
Michael C Lanz ◽  
Evgeny Zatulovskiy ◽  
Matthew P Swaffer ◽  
Lichao Zhang ◽  
Shuyuan Zhang ◽  
...  
Keyword(s):  
Cell Size ◽  
Protein Concentration ◽  
Cell Function ◽  
Size Control ◽  
Cell Physiology ◽  
Proliferating Cells ◽  
Size Dependent ◽  
Large Size ◽  
Concentration Changes ◽  
Proteome Changes

Cell size is tightly controlled in healthy tissues, but it is poorly understood how cell size affects cell physiology. To address this, we measured how the proteome changes with cell size. Protein concentration changes are widespread, depend on the DNA-to-cell size ratio, and are predicted by subcellular localization, size-dependent mRNA concentrations, and protein turnover. As proliferating cells grow larger, concentration changes associated with cellular senescence are increasingly pronounced, suggesting that large size may be a cause rather than just a consequence of cell senescence. Consistent with this hypothesis, larger cells are prone to replicative-, DNA damage-, and CDK4/6i-induced senescence. More broadly, our findings show how cell size could impact many aspects of cell physiology through remodeling the proteome, thereby providing a rationale for cell size control to optimize cell function.

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