scholarly journals A new class of cyclin dependent kinase in Chlamydomonas is required for coupling cell size to cell division

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yubing Li ◽  
Dianyi Liu ◽  
Cristina López-Paz ◽  
Bradley JSC Olson ◽  
James G Umen
Keyword(s):  
Cell Division ◽  
Cell Size ◽  
Mother Cell ◽  
Size Control ◽  
Mitotic Division ◽  
General Mechanism ◽  
Cell Cycle Regulators ◽  
Proliferating Cells ◽  
Multiple Fission ◽  
Division Number

Proliferating cells actively control their size by mechanisms that are poorly understood. The unicellular green alga Chlamydomonas reinhardtii divides by multiple fission, wherein a ‘counting’ mechanism couples mother cell-size to cell division number allowing production of uniform-sized daughters. We identified a sizer protein, CDKG1, that acts through the retinoblastoma (RB) tumor suppressor pathway as a D-cyclin-dependent RB kinase to regulate mitotic counting. Loss of CDKG1 leads to fewer mitotic divisions and large daughters, while mis-expression of CDKG1 causes supernumerous mitotic divisions and small daughters. The concentration of nuclear-localized CDKG1 in pre-mitotic cells is set by mother cell size, and its progressive dilution and degradation with each round of cell division may provide a link between mother cell-size and mitotic division number. Cell-size-dependent accumulation of limiting cell cycle regulators such as CDKG1 is a potentially general mechanism for size control.

scholarly journals A single light-responsive sizer can control multiple-fission cycles in Chlamydomonas

2019 ◽  
Author(s):  
Frank S. Heldt ◽  
John J. Tyson ◽  
Frederick R. Cross ◽  
Béla Novák
Keyword(s):  
Cell Division ◽  
Cell Size ◽  
Mechanistic Model ◽  
Size Control ◽  
Biochemical Network ◽  
Small Cells ◽  
List Type ◽  
Toggle Switch ◽  
Bistable Switch ◽  
Multiple Fission

AbstractProliferating cells need to coordinate cell division and growth to maintain size homeostasis. Any systematic deviation from a balance between growth and division results in progressive changes of cell size over subsequent generations. While most eukaryotic cells execute binary division after a mass doubling, the photosynthetic green alga Chlamydomonas can grow more than eight-fold during daytime before undergoing rapid cycles of DNA replication, mitosis and cell division at night, which produce up to 16 daughter cells. Here, we propose a mechanistic model for multiple fission and size control in Chlamydomonas. The model comprises a light-sensitive and size-dependent biochemical toggle switch that acts as a sizer and guards transitions into and exit from a phase of cell-division cycle oscillations. We show that this simple ‘sizer-oscillator’ arrangement reproduces the experimentally observed features of multiple-fission cycles and the response of Chlamydomonas cells to different light-dark regimes. Our model also makes testable predictions about the dynamical properties of the biochemical network that controls these features and about the network’s makeup. Collectively, these results provide a new perspective on the concept of a ‘commitment point’ during the growth of Chlamydomonas cells and hint at an intriguing continuity of cell-size control in different eukaryotic lineages.Graphical abstractG1-sizer and S/M-oscillator can give rise to multiple-fission cycles in ChlamydomonasLight-responsive bistable switch may guard transition between G1 and S/M-cyclesIllumination increases S/M-entry threshold, causing multiple-fission cyclesDark shift lowers S/M-entry threshold, allowing small cells to commit to fewer divisions

scholarly journals A note on noise suppression in cell-size control

2017 ◽  
Author(s):  
Abhyudai Singh
Keyword(s):  
Cell Division ◽  
Cell Size ◽  
Noise Suppression ◽  
Essential Feature ◽  
Size Control ◽  
Cell Types ◽  
Cellular Growth ◽  
Model Parameters ◽  
Division Rate ◽  
Newborn Size

AbstractDiverse cell types employ mechanisms to maintain size homeostasis and minimize aberrant fluctuations in cell size. It is well known that exponential cellular growth can drive unbounded intercellular variations in cell size, if the timing of cell division is size independent. Hence coupling of division timing to size is an essential feature of size control. We formulate a stochastic model, where exponential cellular growth is coupled with random cell division events, and the rate at which division events occur increases as a power function of cell size. Interestingly, in spite of nonlinearities in the stochastic dynamical model, statistical moments of the newborn cell size can be determined in closed form, providing fundamental limits to suppression of size fluctuations. In particular, formulas reveal that the magnitude of fluctuations in the newborn size is determined by the inverse of the size exponent in the division rate, and this relationship is independent of other model parameters, such as the growth rate. We further expand these results to consider randomness in the partitioning of mother cell size among daughters at the time of division. The sensitivity of newborn size fluctuations to partitioning noise is found to monotonically decrease, and approach a non-zero value, with increasing size exponent in the division rate. Finally, we discuss how our analytical results provide limits on noise control in commonly used models for cell size regulation.

scholarly journals Asymmetry and Aging of Mycobacterial Cells Lead to Variable Growth and Antibiotic Susceptibility

Science ◽  
2011 ◽  
Vol 335 (6064) ◽  
pp. 100-104 ◽  
Author(s):  
Bree B. Aldridge ◽  
Marta Fernandez-Suarez ◽  
Danielle Heller ◽  
Vijay Ambravaneswaran ◽  
Daniel Irimia ◽  
...  
Keyword(s):  
Cell Division ◽  
Environmental Stress ◽  
Cell Size ◽  
Antibiotic Susceptibility ◽  
Mother Cell ◽  
Elongation Rate ◽  
Cell Heterogeneity ◽  
Clonal Population ◽  
Daughter Cells ◽  
Asymmetric Growth

Cells use both deterministic and stochastic mechanisms to generate cell-to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is deterministic heterogeneity in elongation rate that arises because mycobacteria grow in an unusual, unipolar fashion. Division of the asymmetrically growing mother cell gives rise to daughter cells that differ in elongation rate and size. Because the mycobacterial cell division cycle is governed by time, not cell size, rapidly elongating cells do not divide more frequently than slowly elongating cells. The physiologically distinct subpopulations of cells that arise through asymmetric growth and division are differentially susceptible to clinically important classes of antibiotics.

scholarly journals Cell size control driven by the circadian clock and environment in cyanobacteria

2017 ◽  
Author(s):  
Bruno M. C. Martins ◽  
Amy K. Tooke ◽  
Philipp Thomas ◽  
James C. W. Locke
Keyword(s):  
Cell Division ◽  
Circadian Clock ◽  
Cell Size ◽  
Size Control ◽  
Time Lapse ◽  
Complex Interactions ◽  
Light Levels ◽  
Subjective Night ◽  
In The Wild ◽  
Cell Size Control

AbstractHow cells maintain their size has been extensively studied under constant conditions. In the wild, however, cells rarely experience constant environments. Here, we examine how the 24-hour circadian clock and environmental cycles modulate cell size control and division timings in the cyanobacteriumSynechococcus elongatususing single-cell time-lapse microscopy. Under constant light, wild type cells follow an apparent sizer-like principle. Closer inspection reveals that the clock generates two subpopulations, with cells born in the subjective day following different division rules from cells born in subjective night. A stochastic model explains how this behaviour emerges from the interaction of cell size control with the clock. We demonstrate that the clock continuously modulates the probability of cell division throughout day and night, rather than solely applying an on-off gate to division as previously proposed. Iterating between modelling and experiments, we go on to show that the combined effects of the environment and the clock on cell division are explained by an effective coupling function. Under naturally graded light-dark cycles, this coupling shifts cell division away from dusk and dawn, when light levels are low and cell growth is reduced. Our analysis allows us to disentangle, and predict the effects of, the complex interactions between the environment, clock, and cell size control.

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.

scholarly journals Cell Size Control: New Evidence for a General Mechanism

Cell Cycle ◽  
2005 ◽  
Vol 4 (3) ◽  
pp. 418-421 ◽  
Author(s):  
Florian Grebien ◽  
Helmut Dolznig ◽  
Hartmut Beug ◽  
Ernst W. Müllner
Keyword(s):  
Cell Size ◽  
Size Control ◽  
General Mechanism ◽  
Cell Size Control ◽  
New Evidence

scholarly journals Cell size control driven by the circadian clock and environment in cyanobacteria

2018 ◽  
Vol 115 (48) ◽  
pp. E11415-E11424 ◽  
Author(s):  
Bruno M. C. Martins ◽  
Amy K. Tooke ◽  
Philipp Thomas ◽  
James C. W. Locke
Keyword(s):  
Cell Division ◽  
Circadian Clock ◽  
Cell Size ◽  
Time Window ◽  
Size Control ◽  
Time Lapse ◽  
Time Of Day ◽  
Division Rate ◽  
Cell Size Control ◽  
And Shifts

How cells maintain their size has been extensively studied under constant conditions. In the wild, however, cells rarely experience constant environments. Here, we examine how the 24-h circadian clock and environmental cycles modulate cell size control and division timings in the cyanobacteriumSynechococcus elongatususing single-cell time-lapse microscopy. Under constant light, wild-type cells follow an apparent sizer-like principle. Closer inspection reveals that the clock generates two subpopulations, with cells born in the subjective day following different division rules from cells born in subjective night. A stochastic model explains how this behavior emerges from the interaction of cell size control with the clock. We demonstrate that the clock continuously modulates the probability of cell division throughout day and night, rather than solely applying an on−off gate to division, as previously proposed. Iterating between modeling and experiments, we go on to identify an effective coupling of the division rate to time of day through the combined effects of the environment and the clock on cell division. Under naturally graded light−dark cycles, this coupling narrows the time window of cell divisions and shifts divisions away from when light levels are low and cell growth is reduced. Our analysis allows us to disentangle, and predict the effects of, the complex interactions between the environment, clock, and cell size control.

scholarly journals Double or Nothing? Cell Division and Cell Size Control

2019 ◽  
Vol 24 (12) ◽  
pp. 1083-1093 ◽  
Author(s):  
Angharad R. Jones ◽  
Leah R. Band ◽  
James A.H. Murray
Keyword(s):  
Cell Division ◽  
Cell Size ◽  
Size Control ◽  
Cell Size Control
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