For the first time, researchers observe protein degradation in intact brain cells.
Scientists estimate that the human brain consists of about ten to one hundred billions of nerve cells. In order to fulfill their respective tasks as long as possible, these cells have to constantly control their internal proteins with regard to quality and functionality. Otherwise the proteins might clump together and thereby paralyze or even kill the cells. Once the cell recognizes a defect protein, this is marked for degradation and a kind of a molecular shredder, the so-called proteasome, chops it into pieces that are eventually recycled. The study is published in the journal Science.
For the first time now, researchers have succeeded in visualizing this process in intact nerve cells, which previously could only be investigated in the test tube. Electron cryo-tomography was essential for obtaining the described images. Hereby, cells are cooled down to minus 170°C in a fraction of a second. In a consecutive step, pictures of the interior of the cells are taken from many different angles, which then are merged computationally into a three-dimensional image.
In the current study, the use of specific technical innovations allowed the researchers to achieve a unprecedented imaging quality, enabling them to distinguish single proteasomes within the cell. The team state that for the first time it was possible to qualitatively and quantitatively describe this important enzyme complex in intact cells.
In the following experiments, the scientists focused on the activity of the proteasomes. For the interpretation of the single particles it is important to know that there are cap-like structures, the so-called regulatory particles, attached to the ends of proteasomes. They bind proteins that are designated to be degraded and thereby change their shape. The scientists were able to distinguish these states and consequently could deduce how many of the proteasomes were actively degrading proteins.
The researchers summise that in quiescent nerve cells like the ones used in the actual experiments, only a minority of the proteasomes is active. In detail, the results showed that only every fourth proteasome was actively degrading proteins while the rest idled at the same time.
In the future, the scientists want to address the structural changes of the proteasomes under cellular stress as it occurs in neurodegenerative diseases.
Source: Max-Planck-Gesellschaft, München