Learning more about a potential new drug target in heart failure

Inhibitory G protein S-acylation as a therapeutic target in heart failure

Every cell in the body uses small chemical messengers to communicate with their neighbours and the rest of the body. These chemical messengers work by interacting with proteins called receptors that are embedded in the surface of cells. In heart muscle cells, receptors called adrenoceptors link up with molecules called G proteins (called Gai) to control processes such as muscle cell contraction and the switching on of genes. Dr Fuller and his team have previously identified that a specific chemical modification, called S-acylation, allows Gai proteins to focus near the receptor and transmit its message properly in the heart cell. They found decreased amounts of these acylated-G proteins in animals with heart failure. They believe that this prevents Gai from linking up to its adrenoceptor partner, causing heart muscle cells to die and resulting in thickening of the heart wall. In this project, they will investigate how this S-acylation process is altered in healthy and diseased heart muscle. The goal is to identify ways to restore Gai S-acylation, reduce heart muscle cell death and halt the progression to heart failure.