Fig. 6
Schematic summary of the effects of FMP-API-1 and its derivatives on AQP2. AKAPs generally contain protein-protein interactions (PPIs) sites, amphipathic helix domain, and targeting domain48. The amphipathic α-helix enables the anchoring of PKA holoenzymes. The targeting domain mediates the tethering of PKA complexes to selected subcellular compartments. FMP-API-1 and FMP-API-1-1/27 dissociated PKA from AKAPs. The changes in PKA localization increased PKA activity in renal collecting ducts. PKA as well as additional kinases and phosphatases which are interacted with AKAPs through PPIs sites coordinately regulated AQP2 phosphorylation, trafficking, and water transport. In contrast to vasopressin, FMP-API-1/27 increased phosphorylation of AQP2 at S256 in the mouse kidney. FMP-API-1 and FMP-API-1/27 successfully improved urine concentrating ability in the NDI mouse model
