TI - Ezrin-anchored Protein Kinase A Coordinates Phosphorylation -dependent Disassembly of a NHERF1 Ternary Complex to Regulate Hormone -sensitive Phosphate Transport . AB - Congenital defects in the Na/H exchanger regulatory factor-1 ( NHERF1 ) are linked to disordered phosphate homeostasis and skeletal abnormalities in humans . In the kidney , these mutations interrupt parathyroid hormone ( PTH ) -responsive sequestration of the renal phosphate transporter , Npt2a , with ensuing urinary phosphate wasting . We now report that NHERF1 , a modular PDZ domain scaffolding protein , coordinates the assembly of an obligate ternary complex with Npt2a and the PKA-anchoring protein ezrin to facilitate PTH-responsive cAMP signaling events . Activation of ezrin-anchored PKA initiates NHERF1 phosphorylation to disassemble the ternary complex , release Npt2a , and thereby inhibit phosphate transport . Loss-of-function mutations stabilize an inactive NHERF1 conformation that we show is refractory to PKA phosphorylation and impairs assembly of the ternary complex . Compensatory mutations introduced in mutant NHERF1 re-establish the integrity of the ternary complex to permit phosphorylation of NHERF1 and rescue PTH action . These findings offer new insights into a novel macromolecular mechanism for the physiological action of a critical ternary complex , where anchored PKA coordinates the assembly and turnover of the Npt2a-NHERF1-ezrin complex .