Regulated trafficking of aquaporin-2 (AQP2)

(in collaboration with Robert A. Fenton, Aarhus University, DK and Tom Walz, Harvard Medical School, Boston, USA).

Human kidneys filter 180 L of blood daily. Aquaporin-1 molecules bring back 90% of the water to the blood stream, while aquaporin-2 (AQP2) does the remaining 10% in a tightly regulated manner. Malfunction leads to different human diseases. Regulation of AQP2 involves displacement and exocytosis of AQP2-bearing vesicles to the apical membrane of collecting duct principal cells, thereby increasing water flow. This process is controlled by the phosphorylation of several C-terminal amino acid residues of AQP2 induced by vasopressin, a hormone in the blood. Phosphorylated AQP2 recruits yet unknown proteins that form the interface to molecular motors, which execute the vectorial transport of AQP2-vesicles. AQP2 is released from the apical membrane when water homoeostasis is reached, requiring other molecular machines that are regulated by the phosphorylation state of AQP2.

We will identify these components, study their structure, and measure their interactions using cryo-EM, AFM, and single molecule force spectroscopy.