title: Role of collectrin, an ACE2 homologue, in blood pressure homeostasis.
abstract: 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.
authors.affiliation: University of Virginia Health System, Division of Nephrology, Department of Medicine, University of Virginia, PO Box 800133, Charlottesville, VA, 22908, USA.
authors.forename: Pei-Lun
authors.initials: PL
authors.lastname: Chu
authors.forename: Thu H
authors.initials: TH
authors.lastname: Le
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2