Biogenesis of zinc storage granules in Drosophila melanogaster

Membrane transporters and sequestration mechanisms concentrate metal ions differentially into discrete subcellular microenvironments for usage in protein cofactors, signaling, storage, or excretion. Here we identify zinc storage granules as the insect9s major zinc reservoir in principle Malpighian tubule epithelial cells of Drosophila melanogaster . The concerted action of Adaptor Protein-3, Rab32, HOPS and BLOC complexes as well as of the white-scarlet (ABCG2-like) and ZnT35C (ZnT2/ZnT3/ZnT8-like) transporters is required for zinc storage granule biogenesis. Due to lysosome related organelle defects caused by mutations in the homologous human genes, patients with Hermansky-Pudlak syndrome may lack zinc granules in beta pancreatic cells, intestinal paneth cells and presynaptic vesicles of hippocampal mossy fibers.