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Changes in cell morphology are coordinated with cell growth through the TORC1 pathway.

ABSTRACT: Growth rate is determined not only by extracellular cues such as nutrient availability but also by intracellular processes. Changes in cell morphology in budding yeast, mediated by polarization of the actin cytoskeleton, have been shown to reduce cell growth.Here we demonstrate that polarization of the actin cytoskeleton inhibits the highly conserved Target of Rapamycin Complex 1 (TORC1) pathway. This downregulation is suppressed by inactivation of the TORC1 pathway regulatory Iml1 complex, which also regulates TORC1 during nitrogen starvation. We further demonstrate that attenuation of growth is important for cell recovery after conditions of prolonged polarized growth.Our results indicate that extended periods of polarized growth inhibit protein synthesis, mass accumulation, and the increase in cell size at least in part through inhibiting the TORC1 pathway. We speculate that this mechanism serves to coordinate the ability of cells to increase in size with their biosynthetic capacity.

SUBMITTER: Goranov AI

PROVIDER: S-EPMC3880154 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Changes in cell morphology are coordinated with cell growth through the TORC1 pathway.

Goranov Alexi I AI Gulati Amneet A Dephoure Noah N Takahara Terunao T Maeda Tatsuya T Gygi Steven P SP Manalis Scott S Amon Angelika A

Current biology : CB 20130627 14

<h4>Background</h4>Growth rate is determined not only by extracellular cues such as nutrient availability but also by intracellular processes. Changes in cell morphology in budding yeast, mediated by polarization of the actin cytoskeleton, have been shown to reduce cell growth.<h4>Results</h4>Here we demonstrate that polarization of the actin cytoskeleton inhibits the highly conserved Target of Rapamycin Complex 1 (TORC1) pathway. This downregulation is suppressed by inactivation of the TORC1 pa ...[more]

PMID: 23810534

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Project description:Genome size is determined during evolution, but it can also be altered by genetic engineering in laboratories. The systematic characterization of reduced genomes provides valuable insights into the cellular properties that are quantitatively described by the global parameters related to the dynamics of growth and mutation. In the present study, we analyzed a small collection of W3110 Escherichia coli derivatives containing either the wild-type genome or reduced genomes of various lengths to examine whether the mutation rate, a global parameter representing genomic plasticity, was affected by genome reduction. We found that the mutation rates of these cells increased with genome reduction. The correlation between genome length and mutation rate, which has been reported for the evolution of bacteria, was also identified, intriguingly, for genome reduction. Gene function enrichment analysis indicated that the deletion of many of the genes encoding membrane and transport proteins play a role in the mutation rate changes mediated by genome reduction. Furthermore, the increase in the mutation rate with genome reduction was highly associated with a decrease in the growth rate in a nutrition-dependent manner; thus, poorer media showed a larger change that was of higher significance. This negative correlation was strongly supported by experimental evidence that the serial transfer of the reduced genome improved the growth rate and reduced the mutation rate to a large extent. Taken together, the global parameters corresponding to the genome, growth, and mutation showed a coordinated relationship, which might be an essential working principle for balancing the cellular dynamics appropriate to the environment.IMPORTANCE Genome reduction is a powerful approach for investigating the fundamental rules for living systems. Whether genetically disturbed genomes have any specific properties that are different from or similar to those of natively evolved genomes has been under investigation. In the present study, we found that Escherichia coli cells with reduced genomes showed accelerated nucleotide substitution errors (mutation rates), although these cells retained the normal DNA mismatch repair systems. Intriguingly, this finding of correlation between reduced genome size and a higher mutation rate was consistent with the reported evolution of mutation rates. Furthermore, the increased mutation rate was quantitatively associated with a decreased growth rate, indicating that the global parameters related to the genome, growth, and mutation, which represent the amount of genetic information, the efficiency of propagation, and the fidelity of replication, respectively, are dynamically coordinated.

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Changes in cell morphology are coordinated with cell growth through the TORC1 pathway.

Publications

Changes in cell morphology are coordinated with cell growth through the TORC1 pathway.

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