Most stressful situations we encounter in everyday life we don’t want to repeat. But the cellular stress response filmed in this video is worth replaying several times to understand what happens when two cancer cells are stressed.
In this movie of two osteosarcoma cells under severe stress, a set of drop-shaped structures (in green) appears first. This is followed by a second set of droplet-like structures (magenta) and, finally, a fusion of both types of droplets.
These droplets are formed by fluorescently tagged stress response proteins, either G3BP or UBQLN2 (ubiquilin-2). Each protein undergoes a fascinating process called phase separation, which creates a non-membrane-bound compartment in the cytoplasm that restricts the movement of proteins within it. The proteins then fuse with similar proteins to form larger droplets, much like raindrops fuse on a car windshield.
Julia Riley, an undergraduate student in Heidi Henley and Carlos Castaneda’s lab at Syracuse University (New York), funded by the National Institutes of Health (NIH), created this film using sophisticated fluorescence microscopy tools. This is the next in our series in which we showcase the winners of the 2019 Green Fluorescent Protein Image and Video Contest, sponsored by the American Society for Cell Biology. The contest celebrates the discovery of green fluorescent protein (GFP), which, along with a rainbow of other fluorescent proteins, has enabled researchers to visualize proteins and their dynamic activity in cells for the past 25 years.
Riley and colleagues suggest that the phase separation, in this case, is a protective measure that allows the proteins to fight off the rest of the cell under stressful conditions. In this way, proteins can create new functional units within the cell. Researchers are striving to learn much more about what this interesting behavior represents as a basic organizing principle in the cell and how it works.
Most interestingly, similar stress-responsive proteins are often altered in people with the devastating neurological disease amyotrophic lateral sclerosis.ALS is a group of rare neurological diseases in which there is progressive destruction of neurons responsible for volitional movements, such as chewing, walking, and talking. It has been suggested that these split-phase droplets may contribute to the formation of larger protein aggregates that accumulate in the motor neurons of people with this debilitating and potentially fatal disease.
Although the proteins shown in this award-winning video are not mutated forms, Riley is currently working on a sequel that will show versions of the ubiquilin-2 protein, which is found in some people with ALS. He hopes to capture how these mutations can cause another film and what this could mean for understanding ALS.
Learn more from here about Amyotrophic Lateral Sclerosis