WNKs and Sodium Transporter Function in Solute Exchange with Implications for Blood Pressure Regulation as Elucidated through Drosophila.

Like other multicellular organisms, the fruit fly Drosophila melanogaster must maintain homeostasis of the internal milieu, including the maintenance of constant ion and water concentrations. In mammals, the WNK-SPAK/OSR1 (With No Lysine (K)- Ste20-proline/alanine rich kinase/oxidative stress response 1) kinase cascade is an important regulator of epithelial ion transport in the kidney. This pathway regulates SLC12 family cotransporters, including sodium-potassium-2-chloride (NKCC), sodium chloride (NCC) and potassium chloride (KCC) cotransporters. The WNK-SPAK/OSR1 kinase cascade also regulates epithelial ion transport via regulation of the Drosophila NKCC in the Malpighian tubule, the renal epithelium of the fly. Studies in Drosophila have contributed to the understanding of multiple regulators of WNK pathway signaling, including intracellular chloride and potassium, the scaffold protein Mo25, hypertonic stress, hydrostatic pressure, and macromolecular crowding. These will be discussed, together with implications for mammalian kidney function and blood pressure control.