Role of collectrin, an ACE2 homologue, in blood pressure homeostasis.

Collectrin (Tmem27) is a transmembrane glycoprotein that is highly expressed in the kidney and vascular endothelium. It is a homologue of the angiotensin-converting enzyme 2 (ACE2) but harbors no catalytic domain. In the extravascular tissues of the kidney, collectrin is localized to the proximal tubule and collecting duct. Collectrin-deficient mice are featured with hypertension and exaggerated salt sensitivity. These phenotypes are associated with impaired uptake of the nitric oxide precursor L-arginine and the expression of its amino acid transporters, CAT-1 and y(+)LAT1, in endothelial cells. In addition, collectrin-deficient mice display decreased dimerization of nitric oxide synthase and decreased nitric oxide synthesis, but enhanced superoxide generation, suggesting that deletion of collectrin leads to a state of nitric oxide synthase uncoupling. These findings suggest that collectrin plays a protective role against hypertension. The collectrin knockout mouse represents a unique model for hypertension research. Furthermore, collectrin may serve as a novel therapeutic target in the treatment of hypertension.