Cell’s Trash Sorter May Also Act As Signal Messenger, Help Specialized Neurons Sense the Surrounding Environment

As the garbage disposal of the cell, the typical job of the proteasome is to grind down proteins into smaller pieces and recycle some of those bits and parts. For the most part, that is still the case, but researchers studying nerve cells found that the role of proteasome may go well beyond that.

What are Proteasomes?

The cells in our body are full of intricate machines which carry out all kinds of tasks. Some of these machines are analogous to shredders or garbage disposal systems. They destroy cellular components by breaking them down to their constituent parts, which can then be recycled. One such machine is the proteasome.

Proteasome refers to a large protein complex which is responsible for degradation of intracellular proteins. It is a highly sophisticated protease complex which is designed to carry out efficient, selective, and processive hydrolysis of proteins. It is known to work with ubiquitin, which polymerizes to create a marker for regulated proteolysis in eukaryotic cells. Cells in the human body assemble a few different versions of proteasomes, and these versions allow the cells to degrade proteins slightly differently.

Sensory Neuron Modulation

Proteasomes are more complicated than they appear, according to lead author Seth S. Margolis. He and his fellow researchers first discovered proteasomes in the plasma membranes of the neurons of the central nervous system in mice in 2017. They dubbed their discovery as neuronal membrane proteasomes, and have since continued their study on how these special proteasomes promote crosstalk among neurons.

At the time, Margolis' team focused on the central nervous system, particularly the brain and spinal cord. Later, they collaborated with neurobiologist Eric Villalón Landeros who focuses on the peripheral nervous system. This system is a network of neurons that run through the rest of the body and capture sensory information from the environment.

The investigators used mouse antibodies which glom on to proteasomes. This led them to discover proteasomes on the surface of neurons in the dorsal root ganglia, spinal cord, sciatic nerve, and peripheral nerves innervating skin. They were also able to find proteasomes in the same type of peripheral neurons grown in laboratory culture dishes.

Based on their findings, the research discovered that the role of proteasome may shift from trash sorter to signal messenger in dorsal root ganglion neurons. These are special cells which transmit sensory signals from nerve cells close to the skin to the central nervous system.

The new study shows that proteasomes may help these specialized neurons sense the surrounding environment. They can also send signals to each other and differentiate between sensing pain and itch. The research findings can allow experts to better understand the sensory processes and discover new targets for treating pain and other sensory issues.

Since neurons live next to each other for a long time, they require ways to communicate with each other about what they are doing and who they are. Proteasomes present in the membrane of neurons may aid the cells in fine tuning this messaging process.