The Biosynthetic Basis of Cell Size Control - PubMed (original) (raw)

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The Biosynthetic Basis of Cell Size Control

Kurt M Schmoller et al. Trends Cell Biol. 2015 Dec.

Abstract

Cell size is an important physiological trait that sets the scale of all biosynthetic processes. Although physiological studies have revealed that cells actively regulate their size, the molecular mechanisms underlying this regulation have remained unclear. Here we review recent progress in identifying the molecular mechanisms of cell size control. We focus on budding yeast, where cell growth dilutes a cell cycle inhibitor to couple growth and division. We discuss a new model for size control based on the titration of activator and inhibitor molecules whose synthesis rates are differentially dependent on cell size.

Copyright © 2015 Elsevier Ltd. All rights reserved.

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Figures

Figure 1.

Figure 1.. The Size or Number of Many Cellular Components Increases with Cell Size.

Most proteins and mRNAs increase in direct proportion to cell size so that molecular concentrations are constant in growing cells. Moreover, organelle size often scales with cell size. By contrast, cells of different size often have the same amount of genomic DNA. Recently, it was shown that some proteins, including the cell cycle inhibitor Whi5, are not synthesized in proportion to cell size, to generate size-dependent concentrations and couple growth to division.

Figure 2.

Figure 2.. To Link Cell Size with Division, Cells Employ Regulatory Molecules with Cell Size-Dependent Concentrations.

(A) In budding yeast, cell size control is based on the differential synthesis of the cell cycle activator Cln3 and the inhibitor Whi5. While Cln3 is produced in proportion to cell size so that its concentration is constant, Whi5 is produced at a rate independent of cell size so that its concentration is smaller in larger cells. This promotes cell cycle entry in larger cells. (B) In early frog embryos, a similar mechanism senses cell size to control the timing of the mid-blastula transition (MBT) at the 12th division cycle. Histones inhibit the MBT and are at constant concentration while genomic DNA promotes the MBT. DNA concentration doubles at each cell division because in the early frog embryo cells divide without growing. The decreasing histone-to-DNA ratio can then measure cell size to control the timing of the MBT.

Figure 3.

Figure 3.. Origins of Size-Dependent and Size-Independent Protein Synthesis.

(A) The transcription rate of most genes is proportional to cell size. This is consistent with a model where the transcriptional machinery is limiting. Larger cells have more machinery, which results in a higher total rate of transcription. In the case where a haploid and a diploid cell are the same size, the total transcription rate will be the same because in the diploid the machinery is split among twice the number of templates. (B) In contrast to the general case described in (A), the budding yeast cell cycle inhibitor Whi5 is synthesized at a rate independent of cell size. This suggests that Whi5 synthesis is not limited by the transcriptional machinery and is simply proportional to the number of copies of the gene. Indeed, in the case where a haploid and a diploid cell are the same size, Whi5 is synthesized at twice the rate in the diploid.

Figure 4.

Figure 4.. Cell Growth Can Impact Any Component of a Regulatory Network via Specific Size Dependencies in Protein Synthesis.

Schematic illustration of the regulatory network controlling the budding yeast G1/S transition that links cell growth to division. Cell size impacts network activity through the concentration of the central cell cycle inhibitor Whi5, which is diluted by cell growth.

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