Pigment granule biogenesis in drosophila

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During development, cells become specialized to carry out unique functions. One way cells do this is to form membrane-bound organelles that store factors required by that particular cell type. For example, hormone- secreting cells form secretory granules that contain hormones, and nerves form synaptic vesicles that contain neurotransmitters. Defects in formation of membrane organelles typically lead to severe human diseases, many of which are fatal. Different classes of organelles have characteristic morphologies and are produced by distinct membrane trafficking pathways. Much of what we know about mechanisms of membrane and protein transport comes from studies in single cell organisms or cultured cells. Hence, remarkably little is known about how organelles form in developing tissues of a multicellular organism. We use the fruit fly Drosophila melanogaster as a powerful model in which to investigate molecular mechanisms involved in organelle biogenesis. In particular, we have been studying the roles of an important class of membrane lipids, the phosphatidylinositol (PI) phosphates, in membrane trafficking pathways that are important for animal development. Using this system, we uncovered a novel role for PI 4-phosphate (PI4P) and its regulatory enzymes in the formation of pigment granules, which are lysosome-related organelles (LROs) required for normal eye color. We discovered that mutations in the type II PI 4-kinase (PI4KII) or in the PI 4-phosphatase Sac1 cause eye color defects that can be attributed to defects in LRO formation, and we further showed that Sac1 is also required for formation of LROs called melanosomes in mammalian cells. Thus, by studying how PI4P contributes to LRO biogenesis in the well-characterized Drosophila system, our research will provide insight into conserved membrane trafficking pathways involved in normal human development and disease.