Distinct levels in Pom1 gradients limit Cdr2 activity and localization to time and position division

Bhatia, Payal; Hachet, Olivier; Hersch, Micha; Rincón, Sergio A.; Berthelot-Grosjean, Martine; Dalessi, Sascha; Basterra, Laetitia; Bergmann, Sven; Paoletti, Anne; Martin, Sophie G.

doi:10.4161/cc.27411

Cited by 55 publications

(114 citation statements)

References 48 publications

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“…One elegant idea was that a gradient of the Pom1 mitotic inhibitor, which is concentrated at the cell poles and diffuses towards the cell center, might indirectly inhibit mitosis by phosphorylating key mitotic regulator at the cell midzone until the cell grew long enough that the concentration of the Pom1 gradient at the midzone dropped below a critical threshold, allowing mitotic entry [8, 9]. However, subsequent analysis showed despite the size-dependent gradient of Pom1, its level at the midzone does not correlate with mitotic regulation and, furthermore, its function is not required for cell-size regulation [10, 11]. A more recent proposal suggests that Cdr2, the target of Pom1 inhibition, increases in concentration at the midzone as cells grow, and that mitosis is triggered when the concentration of Cdr2, a positive regulator of mitosis, reaches a certain threshold [12].…”

Section: Resultsmentioning

confidence: 99%

Size-Dependent Expression of the Mitotic Activator Cdc25 Suggests a Mechanism of Size Control in Fission Yeast

et al. 2017

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Summary Proper cell size is essential for cellular function. Nonetheless, despite more than 100 years of work on the subject, the mechanisms that maintain cell size homeostasis are largely mysterious [1]. 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 [1, 2]. 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 [3], 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 [4-6]. 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.

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Section: Resultsmentioning

confidence: 99%

Size-Dependent Expression of the Mitotic Activator Cdc25 Suggests a Mechanism of Size Control in Fission Yeast

et al. 2017

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“…Thus, pom1p may affect cdr2p nodes in part by affecting distribution and general properties (such as its mobility in the membrane) of the nodes. Recent studies (published while this work was in press) suggest that cdr2p activity is also regulated by phosphorylation by pom1p and ssp1p protein kinases (Bhatia et al, 2014; Deng et al, 2014). Another important factor in cdr2p localization is likely to be the nucleus that is situated in the cell interior with roughly the same width as the nodal region.…”

Section: Discussionmentioning

confidence: 96%

Cortical regulation of cell size by a sizer cdr2p

Pan

Saunders

Flor-Parra

et al. 2014

eLife

118

194

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Cells can, in principle, control their size by growing to a specified size before commencing cell division. How any cell actually senses its own size remains poorly understood. The fission yeast Schizosaccharomyces pombe are rod-shaped cells that grow to ∼14 µm in length before entering mitosis. In this study, we provide evidence that these cells sense their surface area as part of this size control mechanism. We show that cells enter mitosis at a certain surface area, as opposed to a certain volume or length. A peripheral membrane protein kinase cdr2p has properties of a dose-dependent ‘sizer’ that controls mitotic entry. As cells grow, the local cdr2p concentration in nodes at the medial cortex accumulates as a measure of cell surface area. Our findings, which challenge a previously proposed pom1p gradient model, lead to a new model in which cells sense their size by using cdr2p to probe the surface area over the whole cell and relay this information to the medial cortex.DOI: http://dx.doi.org/10.7554/eLife.02040.001

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“…As a cell grows, the gradient in Pom1 from the poles ensures that its concentration at the mid-cell decreases, which could allow Cdr1 and Cdr2 to inactivate Wee1 and thereby promote mitotic entry. Perturbations of the Pom1 gradient result in both changes to the Cdr2 distribution and cell size (Martin and Berthelot-Grosjean 2009; Moseley et al 2009; Hachet et al 2011; Bhatia et al 2013). …”

Section: Geometric Size Sensing In Fission Yeastmentioning

confidence: 99%

Cell-Size Control

Amodeo

Skotheim

2015

Cold Spring Harb Perspect Biol

156

159

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Cells of a given type maintain a characteristic cell size to function efficiently in their ecological or organismal context. They achieve this through the regulation of growth rates or by actively sensing size and coupling this signal to cell division. We focus this review on potential size-sensing mechanisms, including geometric, external cue, and titration mechanisms. Mechanisms that titrate proteins against DNA are of particular interest because they are consistent with the robust correlation of DNA content and cell size. We review the literature, which suggests that titration mechanisms may underlie cell-size sensing in Xenopus embryos, budding yeast, and Escherichia coli, whereas alternative mechanisms may function in fission yeast.

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Distinct levels in Pom1 gradients limit Cdr2 activity and localization to time and position division

Cited by 55 publications

References 48 publications

Size-Dependent Expression of the Mitotic Activator Cdc25 Suggests a Mechanism of Size Control in Fission Yeast

Size-Dependent Expression of the Mitotic Activator Cdc25 Suggests a Mechanism of Size Control in Fission Yeast

Cortical regulation of cell size by a sizer cdr2p

Cell-Size Control

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