Hydrogel state proteins help cells respond to stimuli

When the cell is stimulated by the external environment (such as heating, starvation), the protein and RNA molecules in the cell will gather with each other to form a mass For a long time, these agglomerations have been considered as a sign of cell damage and harmful dysfunctional molecules, so they need to be removed by cells For example, in the brains of patients with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS), we can observe the accumulation of protein clusters in dying neurons Recently, researchers from the University of Chicago reported in cell that they found that a protein molecule called poly (a) binding protein (PAB1) in budding yeast can respond to external stimuli by forming a mass, helping cells survive 1 Beneficial protein aggregation in this study, the 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 It's like when a fire alarm goes off, people leave their jobs and gather in certain places to ensure safety " "For cells, the formation of hydrogel can not only play a protective role, but also allocate functions, such as calling the firefighters and nursing staff," said Drummond, an assistant professor of University of Chicago in this article 2 the mechanism of stress? 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 process, "phase separation", is necessary for the formation of hydrogels, just like the oil and vinegar in salad dressing, although they are all liquid, they can separate from each other In order to achieve phase separation, previous studies usually used extreme experimental conditions, such as high concentrations of proteins or additives This study shows that when cells are stimulated by the outside world, the normal concentration of PAB1 protein and the normal cell environment can produce phase separation "It's amazing that we don't actually know how these cells feel the temperature changes outside," Drummond said "Animals have neurons that sense the temperature changes, but single celled yeast doesn't The temperature sensitivity of this phase separation process is much greater than that of any other temperature sensing system 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 paper, the researchers suggest that this may be because PAB1 can help to express specific mRNA in response to stimulation, which translates stress proteins to help cells grow In addition to the 3 phase separation process and the disease, researchers are still studying how to disperse Pab1 hydrogel droplets into single molecules Studying the reversal process of phase separation can help us understand why this process fails For example, in neurocytes of patients with neurodegenerative diseases (Alzheimer's disease, ALS, etc.), the presence of protein clumps may be the result of cells responding to stimuli through the phase separation process, which is beneficial But the problem is that the cells can't get these clumps back to their normal state "We found the first evidence that protein clumps might be beneficial," Drummond said "There are more problems we need to solve, such as how cells use the phase separation process to achieve important functions, and how the failure of the reversible process of phase separation leads to diseases."