Alzheimer’s Research: How Proteins Control Information Processing in the Brain

Hall. Mlu. A complex interplay of different proteins is required so that information can reach from one nerve cell to another. Researchers led by Martin Luther University Halle-Wittenberg (MLU) have succeeded in investigating this process in synaptic vesicles, which play a key role in it.

Many billion nerve cells in the body communicate with each other so that people or other living beings can understand their environment and react to it. Countless complex chemical and electrical processes occur within a few milliseconds.

“In synapse of nerve cells, specialized messenger substances – so-called” neurotransmitters “- are released that transmit information between individual nerve cells,” says Jun.-Proc. Dr. Carla Schmidt from the Center for Innovation Competence Helom at MLU. These messengers are packed into small vesicles, synaptic vesicles. In response to an electrical impulse, the latter fuses with the cell membrane and thus releases messengers, which in turn are identified by specialized receptor proteins in the following nerve cells. To do this, many proteins work together, they encapsulate like cogs in a clockwork. Until now, says Schmidt, there is little information about how this process works in detail.

Researchers have now investigated this process with the help of a special form of mass spectrometry. With so-called cross-linking mass spectrometry it is possible to determine the interacting points of proteins. These are mixed with a substance that closely connects proteins to each other. Depending on how proteins interact with each other, this substance reacts at different locations. The mass spectrometer analyzes binding patterns, which can be used to draw conclusions about the arrangement of proteins. In this way, researchers were able to examine the different stages of vesicles and also demonstrate which protein networks were formed.

Halle’s study helps to better understand the process of signal transmission in nerve cells. Knowledge of common processes is the basis for identifying and understanding malfunctions that can trigger diseases such as Alzheimer’s.

The study was supported by the Federal Ministry of Education and Research (BMBF), the European Regional Development Fund (ERDF) and the Alexander von Humboldt Foundation.

About study
Wittig S et al. Cross-linking mass spectrometry exposes protein interactions and functional assemblies in the synaptic vesicle membrane. Nature Communications (2021). DOI: 10.1038 / s41467-021-21102-w