scholarly journals A simple molecular mechanism explains multiple patterns of cell-size regulation

2016 ◽  
Author(s):  
Morgan Delarue ◽  
Daniel Weissman ◽  
Oskar Hallatschek

AbstractIncreasingly accurate and massive data have recently shed light on the fundamental question of how cells maintain a stable size trajectory as they progress through the cell cycle. Microbes seem to use strategies ranging from a pure sizer, where the end of a given phase is triggered when the cell reaches a critical size, to pure adder, where the cell adds a constant size during a phase. Yet the biological origins of the observed spectrum of behavior remain elusive. We analyze a molecular size-control mechanism, based on experimental data from the yeast S. cerevisiae, that gives rise to behaviors smoothly interpolating between adder and sizer. The size-control is obtained from the titration of a repressor protein by an activator protein that accumulates more rapidly with increasing cell size. Strikingly, the size-control is composed of two different regimes: for small initial cell size, the size-control is a sizer, whereas for larger initial cell size, is is an imperfect adder. Our model thus indicates that the adder and critical size behaviors may just be different dynamical regimes of a single simple biophysical mechanism.

2017 ◽  
Author(s):  
Corey A.H. Allard ◽  
Franziska Decker ◽  
Orion D. Weiner ◽  
Jared E. Toettcher ◽  
Brian R. Graziano

SUMMARYCell size drives key aspects of cell physiology, including organelle abundance [1, 2] and DNA ploidy [3]. While cells employ diverse strategies to regulate size [4–11], it is unclear how they are integrated to provide robust, systems-level control. In budding yeast, a molecular size sensor restricts passage of small cells through G1, enabling them to gain proportionally more volume than larger cells before progressing to Start [7, 12, 13]. Size control post-Start is less clear. S/G2/M duration in wildtype cells shows only a weak dependence on cell size; and since yeast exhibit exponential growth, larger cells would be expected to add more volume than smaller ones [7, 14–17]. However, even large mother cells produce smaller daughters, suggesting that additional regulation may occur during S/G2/M [7]. To gain further insight into post-Start size control, we prepared ‘giant’ yeast (>10-fold larger than typical volume) using two approaches to reversibly block cell cycle progression but not growth: optogenetic disruption of the cell polarity factor Bem1 [18, 19] and a temperature-sensitive cdk1 allele [20]. We reasoned that giant yeast would satisfy pre-Start size control while enabling us to uncover post-Start size-limiting mechanisms though the identification of invariant growth parameters. Upon release from their block, giant mothers reenter the cell cycle and their progeny rapidly return to the original unperturbed size. This behavior is consistent with a size-invariant ‘timer’ specifying the duration of S/G2/M and indicates that yeast use at least two distinct mechanisms at different cell cycle phases to ensure size homeostasis.


2013 ◽  
Vol 203 (6) ◽  
pp. 875-881 ◽  
Author(s):  
Clifford P. Brangwynne

The coordinated growth of cells and their organelles is a fundamental and poorly understood problem, with implications for processes ranging from embryonic development to oncogenesis. Recent experiments have shed light on the cell size–dependent assembly of membrane-less cytoplasmic and nucleoplasmic structures, including ribonucleoprotein (RNP) granules and other intracellular bodies. Many of these structures behave as condensed liquid-like phases of the cytoplasm/nucleoplasm. The phase transitions that appear to govern their assembly exhibit an intrinsic dependence on cell size, and may explain the size scaling reported for a number of structures. This size scaling could, in turn, play a role in cell growth and size control.


2000 ◽  
Vol 3 (6) ◽  
pp. 488-492 ◽  
Author(s):  
Eva Kondorosi ◽  
François Roudier ◽  
Emmanuel Gendreau

1988 ◽  
Vol 8 (11) ◽  
pp. 4675-4684 ◽  
Author(s):  
F R Cross

The mating pheromone alpha-factor arrests Saccharomyces cerevisiae MATa cells in the G1 phase of the cell cycle. Size control is also exerted in G1, since cells do not exit G1 until they have attained a critical size. A dominant mutation (DAF1-1) which causes both alpha-factor resistance and small cell size (volume about 0.6-fold that of the wild type) has been isolated and characterized genetically and by molecular cloning. Several alpha-factor-induced mRNAs were induced equivalently in daf1+ and DAF1-1 cells. The DAF1-1 mutation consisted of a termination codon two-thirds of the way through the daf1+ coding sequence. A chromosomal deletion of DAF1 produced by gene transplacement increased cell volume about 1.5-fold; thus, DAF1-1 may be a hyperactive or deregulated allele of a nonessential gene involved in G1 size control. Multiple copies of DAF1-1 also greatly reduced the duration of the G1 phase of the cell cycle.


1982 ◽  
Vol 2 (4) ◽  
pp. 361-368 ◽  
Author(s):  
A E Wheals

By using time-lapse photomicroscopy, the individual cycle times and sizes at bud emergence were measured for a population of saccharomyces cerevisiae cells growing exponentially under balanced growth conditions in a specially constructed filming slide. There was extensive variability in both parameters for daughter and parent cells. The data on 162 pairs of siblings were analyzed for agreement with the predictions of the transition probability hypothesis and the critical-size hypothesis of yeast cell proliferation and also with a model incorporating both of these hypotheses in tandem. None of the models accounted for all of the experimental data, but two models did give good agreement to all of the data. The wobbly tandem model proposes that cells need to attain a critical size, which is very variable, enabling them to enter a start state from which they exit with first order kinetics. The sloppy size control model suggests that cells have an increasing probability per unit time of traversing start as they increase in size, reaching a high plateau value which is less than one. Both models predict that the kinetics of entry into the cell division sequence will strongly depend on variability in birth size and thus will be quite different for daughters and parents of the asymmetrically dividing yeast cells. Mechanisms underlying these models are discussed.


2019 ◽  
Vol 117 (9) ◽  
pp. 1728-1738 ◽  
Author(s):  
Giuseppe Facchetti ◽  
Benjamin Knapp ◽  
Fred Chang ◽  
Martin Howard

1982 ◽  
Vol 92 (1) ◽  
pp. 170-175 ◽  
Author(s):  
M R Kuchka ◽  
J W Jarvik

A mutant of Chlamydomonas reinhardtii with a variable number of flagella per cell has been used to investigate flagellar size control. The mutant and wild-type do not differ in cell size nor in flagellar length, yet the size of the intracellular pool of flagellar precursor protein can differ dramatically among individual mutant cells, with, for example, triflagellate cells having three times the pool of monoflagellate cells. Because cells of the same size, but with very different pool sizes, have flagella of identical length, it appears that the concentration of the unassembled flagellar precursor protein pool does not regulate flagellar length. The relation between cell size, pool size, and flagellar length has also been investigated for wild-type cells of different sizes and ploidies. Again, flagellar length appears to be maintained independent of pool size or concentration.


Author(s):  
David A Guertin ◽  
David M Sabatini

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