The Drosophila Malpighian tubule as a model for mammalian tubule function.

Studies of the genetic model organism, Drosophila melanogaster, have unraveled molecular pathways relevant to human physiology and disease. The Malpighian tubule, the Drosophila renal epithelium, is described here, including tools available to study transport; conserved transporters, channels, and the signaling pathways regulating them; and fly models of kidney stone disease. Tools to measure Malpighian tubule transport continue to advance, including use of a transgenic sensor to quantify intracellular pH and proton fluxes. A recent study generated an RNA-sequencing-based atlas of tissue-specific gene expression, with resulting insights into Malpighian tubule gene expression of transporters and channels. Advances have been made in understanding the molecular physiology of the With No Lysine kinase-Ste20-related proline/alanine rich kinase/oxidative stress response kinase cascade that regulates epithelial ion transport in flies and mammals. New studies in Drosophila kidney stone models have characterized zinc transporters and used Malpighian tubules to study the efficacy of a plant metabolite in decreasing stone burden. Study of the Drosophila Malpighian tubule affords opportunities to better characterize the molecular physiology of epithelial transport mechanisms relevant to mammalian renal physiology.