Characterization of retrograde transport machinery and its relationship to amyotrophic lateral sclerosis (ALS) using the yeast model system

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a rapidly progressive motor neuron disease that causes paralysis and is ultimately fatal. In ALS, motor neurons (nerve cells) are impaired and eventually die. This process breaks the connection between voluntary muscles, which individuals control, and the brain. Other types of brain cells are unaffected, which means patients become paralyzed but their cognitive abilities remain intact. Specialized transport proteins carry survival signals from one end of the neuron to the other. In a mouse model of ALS, the cause of motor neuron disease was found to be due to a mutation in the Vps54 transport protein. In all types of cells, material is transported in a specialized container called a vesicle. In her research, Nicole Quenneville has found that a particular region of the Vps54 transport protein is involved in recognizing the surface of vesicles. It’s this region that is mutated in the mouse model of ALS, suggesting that faulty recognition and transport of these vesicles may lead to motor neuron disease. Using a yeast model, Quenneville is further investigating whether the Vps54 mutation causes transport defects, and whether the mutation changes the interactions that the Vps54 protein has with other proteins. As well, she aims to identify genes and proteins that work with Vps54 to transport molecules within the cell. Quenneville hopes her research will help identify candidate genes for novel therapies, diagnosis, and assessment of susceptibility to ALS.