Cortical regulation of cell size by a sizer cdr2p

Pan, Kally Z.; Saunders, Timothy E.; Flor-Parra, Ignacio; Howard, Martin; Chang, Fred

doi:10.7554/elife.02040

Cited by 120 publications

(224 citation statements)

References 48 publications

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“…In fission yeast, the peripheral membrane protein kinase cdr2p has been reported to regulate cell surface area to a critical value at G2/M (22). In the SAM, our data show that cell surface area and volume are regulated by a mode intermediate between critical size and critical increment.…”

Section: Discussionmentioning

confidence: 48%

“…SAM cells recover their normal mean size following a genetically induced transient size increase, indicating some degree of size regulation (21), although whether size is regulated by the critical size, critical increment, or some other rule remains untested. Further, it is not known if size regulation acts upon cell volume, surface area [as reported for fission yeast (22)], or some other metric (e.g., anticlinal surface area). Moreover, whether size regulation is dependent on cellular parameters such as cell shape or growth rate, tissue-level properties such as cellcell contact topology, or position within the SAM has not been determined.…”

mentioning

confidence: 99%

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Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Willis

Refahi

Wightman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

186

217

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Cell size and growth kinetics are fundamental cellular properties with important physiological implications. Classical studies on yeast, and recently on bacteria, have identified rules for cell size regulation in single cells, but in the more complex environment of multicellular tissues, data have been lacking. In this study, to characterize cell size and growth regulation in a multicellular context, we developed a 4D imaging pipeline and applied it to track and quantify epidermal cells over 3-4 d in Arabidopsis thaliana shoot apical meristems. We found that a cell size checkpoint is not the trigger for G2/M or cytokinesis, refuting the unexamined assumption that meristematic cells trigger cell cycle phases upon reaching a critical size. Our data also rule out models in which cells undergo G2/M at a fixed time after birth, or by adding a critical size increment between G2/M transitions. Rather, cell size regulation was intermediate between the critical size and critical increment paradigms, meaning that cell size fluctuations decay by ∼75% in one generation compared with 100% (critical size) and 50% (critical increment). Notably, this behavior was independent of local cell-cell contact topologies and of position within the tissue. Cells grew exponentially throughout the first >80% of the cell cycle, but following an asymmetrical division, the small daughter grew at a faster exponential rate than the large daughter, an observation that potentially challenges present models of growth regulation. These growth and division behaviors place strong constraints on quantitative mechanistic descriptions of the cell cycle and growth control.cell size | cell growth | cell cycle | homeostasis | plant stem cells H ow cells coordinate growth and division to achieve a particular cell size remains a fundamental question in biology. Our understanding of this basic property of cells is limited, in part, by the lack of quantitative data on cellular growth and size kinetics over multiple generations, especially in higher eukaryotes (1). Classical studies of cell size homeostasis focused on whether division occurred upon reaching a critical size or after a fixed time period has elapsed (2, 3). However, time-lapse studies of single-celled organisms spanning a range of bacteria (4-7) and the yeast Saccharomyces cerevisiae (8) have recently indicated that cell size is regulated by the addition of a fixed volume increment between divisions. Identification of the size regulation behavior constrains the set of feasible molecular scenarios for how growth and division are coordinated with the cell cycle (8-10). In multicellular tissues, the loss of growth and division/cell cycle coordination could have an impact on the organism's development, yet, to the best of our knowledge, cell growth and size kinetics have never before been measured over generations in a tissue context. The experimental challenges are particularly acute because interdivision times are often on the order of tens of hours, cells have a diversity of shapes necessitating di...

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Section: Discussionmentioning

confidence: 48%

mentioning

confidence: 99%

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Willis

Refahi

Wightman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

186

217

View full text Add to dashboard Cite

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“…Such global feedback could impact on cellular 'sizing' mechanisms that are required for correct cell size homeostasis. In the fission yeast Schizosaccharomyces pombe, the protein kinase Cdr2p accumulates at the medial cellular cortex proportionally to the cell surface area and contributes to size control [23]. Mathematical modelling that assumes constant concentration of Cdr2p during cell elongation explains the above experimental observation.…”

Section: Global Feedback and Cell Sizementioning

confidence: 91%

“…Mathematical modelling that assumes constant concentration of Cdr2p during cell elongation explains the above experimental observation. Therefore it is crucial that Cdr2p expression levels precisely scale with cell volume to ensure proper sizing [23]. Cdr2p acts in a network of other factors that includes Pom1p [24,25].…”

Section: Global Feedback and Cell Sizementioning

confidence: 99%

Connecting growth with gene expression: of noise and numbers

Shahrezaei

Marguerat²

2015

Current Opinion in Microbiology

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Growth is a dynamic process whereby cells accumulate mass. Growth rates of single cells are connected to RNA and protein synthesis rates, and therefore with biomolecule numbers. Noise in gene expression depends on these numbers, and is thus linked with cellular growth. Whether these global attributes of the cell participate in gene regulation is still largely unexplored. New experimental and modelling studies suggest that systemic variations in biomolecule numbers can coordinate cellular processes, including growth itself, through global regulatory feedback that acts in addition to genetic regulatory networks. Here, we review these findings and speculate on possible implications of this less appreciated layer of gene regulation for cellular physiology and adaptation to changing environments.

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“…2C). These inhibitory gradients help guide accumulation of division initiators at midcell Pan et al 2014;Rincon et al 2014). A somewhat similar mechanism operates in Escherichia coli, where the MinCDE system relies on an oscillatory pattern of division inhibitor localization at the two cell poles (Hu et al 1999;Raskin and de Boer 1999).…”

Section: Intracellular Scaling Mechanismsmentioning

confidence: 93%

Intracellular Scaling Mechanisms

Reber

Goehring

2015

Cold Spring Harb Perspect Biol

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Organelle function is often directly related to organelle size. However, it is not necessarily absolute size but the organelle-to-cell-size ratio that is critical. Larger cells generally have increased metabolic demands, must segregate DNA over larger distances, and require larger cytokinetic rings to divide. Thus, organelles often must scale to the size of the cell. The need for scaling is particularly acute during early development during which cell size can change rapidly. Here, we highlight scaling mechanisms for cellular structures as diverse as centrosomes, nuclei, and the mitotic spindle, and distinguish them from more general mechanisms of size control. In some cases, scaling is a consequence of the underlying mechanism of organelle size control. In others, size-control mechanisms are not obviously related to cell size, implying that scaling results indirectly from cell-size-dependent regulation of sizecontrol mechanisms.

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Cortical regulation of cell size by a sizer cdr2p

Cited by 120 publications

References 48 publications

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Connecting growth with gene expression: of noise and numbers

Intracellular Scaling Mechanisms

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