Cloning and expression of an ATP-regulated human retina C-type natriuretic factor receptor guanylate cyclase

The natriuretic factors are structurally related polypeptide hormones that regulate the hemodynamics of the physiological processes of diuresis, water balance, and blood pressure. Presumably, these hormones act through the activation of guanylate cyclases which are also the specific receptors of these hormones. Two such structurally similar cell surface receptors are known; the ligand for one is atrial natriuretic factor (ANF) and for the other is C-type natriuretic peptide (CNP). Studies with ANF receptor guanylate cyclase (ANF-RGC) have indicated that its ligand binding site is extracellular and the catalytic site is intracellular, but the mere ligand binding to the receptor domain does not activate the cytosolic catalytic domain. An intervening ATP-mediated event is obligatory: ATP binds to a defined ATP-regulated module (ARM) sequence and bridges the events of ligand binding and signal transduction. The mechanism of CNP signaling is not known, although CNP in intact cells transfected with CNP receptor guanylate cyclase (CNP-RGC) stimulates the formation of cyclic GMP. Furthermore, there is no prior evidence of the presence of CNP signal transduction system in retina, although the presence of ANF-RGC has been documented. We now report the molecular cloning and expression of CNP-RGC from human retina and show that ATP is obligatory in CNP signaling also.(ABSTRACT TRUNCATED AT 250 WORDS)