THE BARS-DEPENDENT MEMBRANE FISSION MACHINERY IN THE GOLGI COMPLEX. RELEVANCE IN MEMBRANE TRANSPORT-RELATED DISEASES

A number of genetic diseases arise from defects in gene products (proteins) that result in their incorrect delivery to their sites of action in cells. The correct functioning of this transport of proteins in cells is essential for the movement of newly synthesized proteins from their site of synthesis to their site of function. As this occurs through a number of membrane organelles that receive, process and send on membrane “packages”, or carriers, that contain proteins destined for specific compartments, understanding the mechanisms behind the arrival and the departure of these carriers would allow us to manipulate these processes as needed. One such mechanism is the pinching off, or fissioning, of these carriers. Our aim is that through our studies of a protein called BARS, which we have seen to be an essential component of this fissioning process in specific steps of protein transport, we will be able to move towards a better understanding of how membrane fissioning occurs. This will have important pathophysiological consequences as it will then enable us to search for small molecules (drugs) that can be used to manipulate these pathways in genetic diseases that arise from defects in protein delivery. This will thus enable us to move towards the design of drugs that can be used to stimulate or inhibit protein transport in genetic diseases such as: autosomal dominant polycystic kidney disease, which causes kidney failure in children and adults; ataxia telangiectasia, a neurodegenerative childhood disease that affects the brain and other body systems; and Lowe syndrome (oculocerebrorenal syndrome), a condition affecting the eyes, brain and kidney that causes physical and mental handicaps in children. We thus expect that these studies will be relevant for the comprehension and treatments of a number of genetic diseases that are caused by defects in protein traffic.