Identification of factors that regulate AP3-dependent transport

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The cell consists of many different compartments, each carrying out a distinct function. For example, the "lysosome" can be thought of as the cell's recycling centre, since it contains enzymes that break down unwanted proteins so their components can be re-used to make new proteins. In addition to getting rid of unwanted molecules, special types of lysosomes serve as storage compartments for proteins needed for immunity, blood clotting, and brain function. The enzymes that recycle proteins inside lysosomes are first manufactured in a different compartment called the "Golgi". These enzymes are then moved from the Golgi to the lysosome in small containers called "vesicles". It is very important that the correct protein is sorted into the right vesicle so it can be delivered to the right place. This task is generally fulfilled by a group of proteins, called Adaptor Protein complexes, which recognize cargo molecules for transport and initiate the process that will take them to their final destination. A specific type of Adaptor Protein complex, AP-3, is required for the formation and function of lysosomes. However, Adaptor Proteins cannot work by themselves. Other types of Adaptors have regulators that guide them to the correct location and activate them for cargo binding, but so far no regulators for AP-3 have been found. We use yeast as a model system to identify these regulators and understand how they work. Although yeast is a simple organism, the yeast AP-3 regulates a strikingly similar pathway to the vacuole, the yeast version of the human lysosome. As a result, yeast is an excellent resource for identifying the genes involved in the complex transport pathways that operate in humans. The simple nature of the yeast genome also allows us to obtain a 'snapshot' view of all the genes that are cooperating to regulate a cellular pathway. This will tell us which genes in humans might also work with AP-3, and how the pathway they regulate might lead to the formation of lysosomes.