Disorders of pigmentation are common and contribute to significant psychosocial illness, particularly in dark-skinned people. Dramatic advances in the understanding the biochemistry of melanin synthesis and its controlling genes have been made in the past years. Unfortunately, little known, or being investigated, about the basic cell biology of the melanocyte. I propose a project that begins to investigate melanocyte biology, by looking at the targeting of intracellular vesicular compartments. Melanogenesis is dependent on the accurate formation, movement and fusion of these compartments within the melanocyte. Rab proteins, small ras-like GTP binding proteins, play a key role in vesicle formation and targeting. Some rabs are cell-specific, while others are subcellular compartment or vesicle type specific. Melanocytes have not been examined for rab proteins or the role they most assuredly play in melanogenesis. It will identify rab proteins in melanocytes and determine their locations within the cell. Additionally, I will modify an in vitro reconstitution system to study intracellular transport, and begin to examine the role of rab proteins in processes that are critical to melanin formation. The ultimate goal is to identify components of melanocyte intracellular trafficking and to understand how their disruption contributes to disease states.
