Functional Role of ATRAP, a Novel Receptor Binding Protein, in the Regulation of Renal Sodium Handling and Blood Pressure

Abstract

Pathological activation of renal angiotensin II （Ang II） type 1 receptor （AT1R） signaling stimulates renal tubular sodium transporters including epithelial sodium channel to increase renal sodium reabsorption. In the course of an investigational search for a means to functionally and selectively modulate AT1R signaling for that purpose, a molecule directly interacting with the carboxyl-terminal cytoplasmic domain of AT1R was identified by employing yeast two-hybrid screening of a mouse kidney cDNA library and named AT1R-associated protein （ATRAP）. We showed that ATRAP promotes constitutive AT1R internalization so as to inhibit pathological AT1R activation in response to certain stimuli. In the kidney, ATRAP is abundantly distributed in epithelial cells along the renal tubules. The results employing genetic engineered mice with modified ATRAP expression showed that ATRAP plays a key role in the regulation of renal sodium handling and the modulation of blood pressure in response to pathological stimuli such as chronic Ang II infusion, dietary high salt loading and 5/6 nephrectomy, and suggest ATRAP to be a target of interest.