When cells are stimulated by external environment (such as heating and starvation), the proteins and RNA molecules in the cell will aggregate together to form clumps. For a long time, these clumps are considered to be markers of cell damage and are malfunctioning and malfunctioning molecules, and therefore need to be removed by cells. For example, in the brain of patients with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS), we can all observe the accumulation of proteins in the dying neurons. Recently, researchers at the University of Chicago in the Cell said they found that a protein molecule called the poly (A) binding protein (Pab1) in the bud yeast can react to the external stimulus by forming a lump to help the cell survive the difficulty.
1. beneficial protein aggregation
In this study, researchers tried to separate the Pab1 masses. Under the microscope, the clusters look like round drops, rather than lumps, rather than hydrogels, which resemble jelly or toothpaste. Most importantly, when researchers interfere with the formation of such hydrogels in living cells, these cells lose the ability to respond to external stimuli. That is to say, the formation of Pab1 hydrogel not only does not damage the normal function of cells, but also enhances the adaptability of cells.
"The aggregation of this protein is more like an organized emergency procedure. Just like a fire alarm, people leave their jobs and assemble in specific places to ensure safety. "For cells, the formation of hydrogels can not only play a protective role, but also function, such as calling firefighters and nurses," said Drummond, an assistant professor at University of Chicago.
2. stress mechanism? - phase separation
In recent years, a large number of studies have shown that the formation of protein droplets and hydrogels is an important way of cell organization and remodeling itself. One of these processes, "phase separation", is necessary for the formation of hydrogels, like oil and vinegar in the salad dressing, which, though liquid, can be separated from each other. In order to occur phase separation, previous studies usually use extreme experimental conditions, such as high concentrations of protein or additives. This study shows that cells can undergo phase separation during normal stimulation of Pab1 protein and normal cell environment.
"Surprisingly, we don't really know how these cells feel the temperature changes in the outside world," Drummond said. "Animals have neurons that respond to temperature changes, but single cell yeasts do not. The temperature sensitivity of the phase separation process is much greater than that of any other temperature sensing system described. Therefore, we hypothesize that the mechanism by which hydrogel can induce external temperature and other stimuli may be widespread.
Drummond and his colleagues are continuing to study how this phase separation process helps cells survive under stimulation. In the article, the researchers suggest that this may be because Pab1 can help express specific mRNA in response to stimulus, which translates stress proteins to help cell growth.
The inverse process and disease of 3. phase separation
In addition, researchers are still studying how to disperse Pab1 hydrogel droplets into single molecules. Studying the reverse process of phase separation can help us understand why this process fails. For example, in the nerve cells of patients with neurodegenerative diseases (Alzheimer's disease, ALS, etc.), the presence of protein mass may be beneficial for the cell use phase separation process to respond to the results of stimulation. But the problem is that cells can't get these masses back to their normal state.
"We have found the first evidence that the protein mass may be beneficial," Drummond said. "There are more questions that need us to solve, such as how cells use the phase separation process to achieve important functions, and how the phase separation of the reversible process causes disease."