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 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 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 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 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 Synergistic CDK control pathways maintain cell size homeostasis

2020 ◽  
Author(s):  
James O. Patterson ◽  
Souradeep Basu ◽  
Paul Rees ◽  
Paul Nurse
Keyword(s):  
Cell Division ◽  
Cell Size ◽  
High Throughput ◽  
Small Cells ◽  
Control Network ◽  
Size Information ◽  
Division Cell ◽  
Diploid Cells ◽  
High Cyclin

AbstractTo coordinate cell size with cell division, cell size must be computed by the cyclin-CDK control network to trigger division appropriately. Here we dissect determinants of cyclin-CDK activity using a novel high-throughput single-cell in vivo system. We show that inhibitory phosphorylation of CDK encodes cell size information and works synergistically with PP2A to prevent division in smaller cells. However, even in the absence of all canonical regulators of cyclin-CDK, small cells with high cyclin-CDK levels are restricted from dividing. We find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by DNA concentration. Thus, multiple pathways directly regulate cyclin-CDK activity to maintain robust cell size homeostasis.

scholarly journals Growth Rate and Cell Size Modulate the Synthesis of, and Requirement for, G1-Phase Cyclins at Start

2004 ◽  
Vol 24 (24) ◽  
pp. 10802-10813 ◽  
Author(s):  
Brandt L. Schneider ◽  
Jian Zhang ◽  
J. Markwardt ◽  
George Tokiwa ◽  
Tom Volpe ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Rate ◽  
Cell Size ◽  
Cell Cycle Progression ◽  
Control Mechanism ◽  
Size Control ◽  
Small Cells ◽  
Critical Threshold ◽  
Cycle Progression

ABSTRACT In Saccharomyces cerevisiae, commitment to cell cycle progression occurs at Start. Progression past Start requires cell growth and protein synthesis, a minimum cell size, and G1-phase cyclins. We examined the relationships among these factors. Rapidly growing cells expressed, and required, dramatically more Cln protein than did slowly growing cells. To clarify the role of cell size, we expressed defined amounts of CLN mRNA in cells of different sizes. When Cln was expressed at nearly physiological levels, a critical threshold of Cln expression was required for cell cycle progression, and this critical threshold varied with both cell size and growth rate: as cells grew larger, they needed less CLN mRNA, but as cells grew faster, they needed more Cln protein. At least in part, large cells had a reduced requirement for CLN mRNA because large cells generated more Cln protein per unit of mRNA than did small cells. When Cln was overexpressed, it was capable of promoting Start rapidly, regardless of cell size or growth rate. In summary, the amount of Cln required for Start depends dramatically on both cell size and growth rate. Large cells generate more Cln1 or Cln2 protein for a given amount of CLN mRNA, suggesting the existence of a novel posttranscriptional size control mechanism.

scholarly journals Relationship among Several Key Cell Cycle Events in the Developmental Cyanobacterium Anabaena sp. Strain PCC 7120

2006 ◽  
Vol 188 (16) ◽  
pp. 5958-5965 ◽  
Author(s):  
Samer Sakr ◽  
Melilotus Thyssen ◽  
Michel Denis ◽  
Cheng-Cai Zhang
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Division ◽  
Cell Growth ◽  
Cell Size ◽  
Dna Content ◽  
Small Cells ◽  
Filamentous Cyanobacterium ◽  
Pcc 7120 ◽  
Heterocyst Development

ABSTRACT When grown in the absence of a source of combined nitrogen, the filamentous cyanobacterium Anabaena sp. strain PCC 7120 develops, within 24 h, a differentiated cell type called a heterocyst that is specifically involved in the fixation of N2. Cell division is required for heterocyst development, suggesting that the cell cycle could control this developmental process. In this study, we investigated several key events of the cell cycle, such as cell growth, DNA synthesis, and cell division, and explored their relationships to heterocyst development. The results of analyses by flow cytometry indicated that the DNA content increased as the cell size expanded during cell growth. The DNA content of heterocysts corresponded to the subpopulation of vegetative cells that had a big cell size, presumably those at the late stages of cell growth. Consistent with these results, most proheterocysts exhibited two nucleoids, which were resolved into a single nucleoid in most mature heterocysts. The ring structure of FtsZ, a protein required for the initiation of bacterial cell division, was present predominantly in big cells and rarely in small cells. When cell division was inhibited and consequently cells became elongated, little change in DNA content was found by measurement using flow cytometry, suggesting that inhibition of cell division may block further synthesis of DNA. The overexpression of minC, which encodes an inhibitor of FtsZ polymerization, led to the inhibition of cell division, but cells expanded in spherical form to become giant cells; structures with several cells attached together in the form of a cloverleaf could be seen frequently. These results may indicate that the relative amounts of FtsZ and MinC affect not only cell division but also the placement of the cell division planes and the cell morphology. MinC overexpression blocked heterocyst differentiation, consistent with the requirement of cell division in the control of heterocyst development.

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.

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