Break the textbook conclusion! Cells avoid multitasking

Textbooks tell you that in dividing cells, the production of new DNA peaks in S phase, while the production of other macromolecules, such as proteins, lipids and polysaccharides, continues at more or less the same level. Molecular biologists at the University of Groningen led by Prof. Matt

Textbooks tell you that in dividing cells, the production of new DNA peaks in S phase, while the production of other macromolecules, such as proteins, lipids and polysaccharides, continues at more or less the same level. Molecular biologists at the University of Groningen led by Prof. Matthias Heinemann have now discovered that this is not the case: The synthesis of proteins shows two peaks, whereas the synthesis of lipids reaches a single peak. These transitions could explain the metabolic shocks that lead to cell division, which the group had previously identified. Their new results were published in Nature Metabolism on February 27.

 

Every dividing eukaryotic cell goes through a cell cycle: a growth phase (G1) to a phase of synthesis of new DNA (S), an interstitial phase (G2), and finally the cell division phase of mitosis (M). The academic literature on cell division will tell you that, apart from the synthesis of DNA, all other molecules in the cell, such as proteins, lipids and polysaccharides, are produced at a more or less constant rate throughout the cell cycle phases.

 

Seven years ago, Matthias Heinemann and his team described oscillations in cellular metabolism, which appear to be the process that coordinates eukaryotic cell division. His team has now studied metabolism in more detail and measured the rate at which proteins, lipids and polysaccharides are produced during the cell cycle. They found that the textbook was wrong.

 

"We used dynamic microscopic measurements in single cells to show how the production of different macromolecules peaks at different times," explains Heinemann. The basal rate of protein synthesis peaks in the G1 phase, declines in the S phase, and increases at the end of the cell cycle. It peaks again in the second half. We also found that there is only one peak in the synthesis of lipids and polysaccharides that make up the cell wall, and that is in the second half."

 

To determine the rate of protein synthesis, the scientists used an established method of monitoring fluorescent proteins. They also devised a second, more sophisticated approach, by which they could verify that protein production appeared to follow a two-wave pattern.

 

Vakil Takhaveev, first author of the article, said, "We had to develop a second method because our results contradicted what we and others knew about cell cycle metabolism. Using this new approach, we probe the sensitivity of cells to inhibitors of protein biosynthesis at each moment in the cell cycle. It turns out that this sensitivity peaks at different stages of the cell cycle.”

 

In their paper, Heinemann and his team show that the different components of the cell are not produced simultaneously. Furthermore, the researchers show that the entire central metabolism must change to accommodate the production of such temporally separated building blocks. For example, they found that rates of glucose consumption, ethanol excretion, and respiration were assigned to specific phases of the cell cycle.

 

Interestingly, these new measurements are consistent with their earlier findings, Heinemann explains: "Cells have to activate different biosynthetic pathways to produce amino acids or lipids. This produces changes in the flux of metabolites, which explains why we have previously identified metabolic oscillations during cell division. However, this leaves the question of exactly how and why this happens."

 

"At the moment, one aspect we can only speculate on is that if a cell is just growing, all the building blocks need to be going on at the same time," says Heinemann. “But during division, the situation is more complicated. It may well be that the order of production helps the cell divide.”

 

Osmolality may be the key. "Imagine blowing up a balloon. At first, you need very high pressure, but once it starts to inflate, lower pressure is enough. Maybe the cells first make a lot of protein to increase the osmotic pressure inside the cell, which might help separating daughter cells. This is just speculation, but I do feel that there is a biophysical reason behind the patterns we observed."

 

He will continue to investigate these ideas and search for the regulatory mechanisms responsible for the different stages of the synthesis of cellular building blocks. "We don't yet know how this works, but it will be very interesting to find out and see how these regulatory systems are perturbed. The current findings and future work are necessary for a fundamental understanding of cell physiology, and ultimately will help us tackle cancer and aging.”


Anna Bryan

1 Blog posts

Comments