Scientists have made a surprising discovery about a major immune regulator known as the STING protein, which could open up new possibilities for developing treatments for various diseases.
STING, which stands for stimulator of interferon genes, plays a crucial role in the human immune system. It identifies cellular danger signals, such as viral DNA or damaged tissue, and triggers various defense mechanisms. These mechanisms include producing interferons to combat infections and activating inflammasome and non-canonical autophagy to eliminate harmful substances and pathogens.
However, the process by which STING stimulates these mechanisms has been poorly understood. Until now, it was believed that STING functioned as a molecular switch that activated various pathways depending on the type of danger signal it encountered.
Researchers at MIT and Harvard Medical School have discovered that STING has an unexpected and previously unidentified role: It can function as an ion channel, enabling protons to escape from a cell organelle called the Golgi body. This establishes it as the initial human immune sensor capable of converting danger signals into ion flow.
The Golgi apparatus is a cellular structure that sorts and alters proteins and other molecules. It contains a high level of protons, positively charged particles, within its membrane. Upon detecting DNA, STING opens a channel, enabling some protons to exit, thus generating an electrical current. This current subsequently activates the inflammasome and non-canonical autophagy, aiding in the removal of DNA and any linked pathogens.
The researchers found this new function for STING using a method called patch-clamp electrophysiology, which measures the electrical activity of individual cells or cell parts. They also utilized genetic engineering and pharmacological tools to control STING and its pathways.
“Arriving at this new idea that STING is a proton channel required connecting prior findings by other labs that either STING or proton flux could activate the inflammasome and non-canonical autophagy, which led us to hypothesize that STING initiates or mediates proton flux to trigger both downstream processes,” the researchers said in a statement.
The identification of STING’s ion channel function opens up new possibilities for developing therapeutics to regulate STING. This is crucial as STING plays a role in numerous diseases, including autoimmune disorders, cancer, and infectious diseases. For instance, increasing STING’s activity could improve the immune response to tumors or viruses, while decreasing its activity could alleviate inflammation or tissue damage.
The researchers anticipate that their discovery will encourage additional research on STING and its impact on the immune system, as well as the creation of new medications targeting STING’s ion channel activity.
Relevant articles:
– National Center for Biotechnology Information
– National Center for Biotechnology Information – Wikipedia
– Study finds a surprising new role for a major immune regulator