Researchers have advanced their understanding of how drugs interact with connexin molecules. Connexins create channels that enable direct communication between adjacent cells. Dysfunctions in these channels play a role in neurological and cardiac disorders. This enhanced knowledge of drug binding and action on connexins could aid in developing treatments for these diseases.
Today we use many electronic means to communicate, but sometimes dropping a note in a neighbor’s letter box or leaving a cake on a doorstep is most effective. Cells too have ways to send direct messages to their neighbors.
Adjacent cells can communicate directly through relatively large channels called gap junctions, which allow cells to freely exchange small molecules and ions with each other or with the outside environment. In this way, they can coordinate activities in the tissues or organs that they compose and maintain homeostasis.
Such channels are created from proteins known as connexins. Six connexins situated in the cell membrane create a hemichannel; this hemichannel joins with a hemichannel in a neighboring cell to create a two-way channel.
When connexin channels do not work properly, they cause changes in intercellular communication that have been linked to many different diseases. These include cardiac arrhythmias, diseases of the central nervous system such as epilepsy, neurodegenerative diseases, and cancer.
As a result, the search is on for drugs that target connexins. Yet, understanding of the structure of connexins and how drugs bind to connexin channels to block or activate them is limited. Indeed, of the twenty-one types of connexins known to exist in humans, few of them are currently evaluated as drug targets.
An explanation for antimalarial side effects?
Now, researchers from PSI, ETH Zurich, and the University of Geneva have deepened our understanding of connexin channels and how they bind to drug molecules. The study is published in the journal Cell Discovery.
The connexin they studied is known as connexin-36, or Cx36 for short. Cx36 plays important roles in the pancreas and the brain, respectively controlling DOI: 10.1038/s41421-024-00691-y