Researchers at Johns Hopkins Medicine have discovered that the proteasome, typically known as the garbage disposal of the cell, may have a role beyond breaking down proteins. They found that proteasomes in dorsal root ganglion neurons, which transmit sensory signals, may also have a role in sensing the surrounding environment and facilitating communication between neurons. This discovery could help scientists better understand sensory processes and potentially identify new targets for treating pain and other sensory issues.
The researchers, led by Dr. Seth S. Margolis, first identified proteasomes in the membranes of central nervous system neurons in 2017. They continued studying these proteasomes, known as neuronal membrane proteasomes, to understand how they promote messaging and crosstalk among neurons. Collaborating with neurobiologist Dr. Eric Villalón Landeros, they investigated whether proteasomes could also be found in peripheral neurons, which capture sensory information closer to the skin.
Using mouse antibodies and other methods, the researchers confirmed the presence of proteasomes on the surface of neurons in various parts of the nervous system, including the spinal cord, dorsal root ganglia, sciatic nerve, and peripheral nerves innervating the skin. They also found proteasomes in peripheral neurons grown in the lab. By blocking the function of neuronal membrane proteasomes in mice with a specific inhibitor, the researchers observed a decrease in sensory responses, suggesting that these proteasomes play a crucial role in sensation and signaling.
Further analysis using single cell sequencing technology revealed that membrane proteasomes were expressed in a subpopulation of neurons involved in itch sensation and histamine sensitivity. When the researchers blocked their proteasomes in both itch-related and non-itch related neurons, they observed changes in cell activity, indicating that proteasomes facilitate cross talk between these cells. This finding could have implications for understanding and potentially manipulating sensory responses related to pain and itch.
Currently, proteasome blockers like Velcade are used to treat certain types of cancer. The researchers plan to continue investigating how neuronal membrane proteasomes function in sensory neurons and whether they can be manipulated to influence pain and itch sensation. By understanding the role of proteasomes in sensory processes, scientists may identify new therapeutic targets for addressing pain and other sensory disorders. The study was funded by the National Institutes of Health and a grant from the Merkin Peripheral Neuropathy and Nerve Regeneration Center.
