Corin: new insights into the natriuretic peptide system

Abstract

Natriuretic peptides are important in regulating salt and body-fluid balance. In cells, these peptides are made as precursor forms that are converted to active forms by proteolyic processing. Corin is a transmembrane serine protease identified in the heart. Corin converts pro-atrial natriuretic peptide (pro-ANP) to active ANP in a sequence-specific manner. In mice, lack of corin prevents the conversion of pro-ANP to ANP and causes salt-sensitive hypertension. The hypertensive phenotype is exacerbated when the mice become pregnant. In humans, single nucleotide polymorphisms in the corin gene have been identified in African Americans with hypertension and cardiac hypertrophy. These data indicate that corin is important in maintaining normal blood pressure in vivo and that corin deficiency may contribute to hypertension and heart disease in patients.

Figure 1. Processing of natriuretic peptides

Natriuretic peptides are synthesized as prepropeptides. The signal peptide (sp) is removed by signal peptidase. The propeptide is cleaved by propeptide convertase to produce an inactive N-terminal peptide and a C-terminal mature peptide that is biologically active.

Figure 2. Corin domain sturecture and mRNA expression in the heart

Corin has a transmembrane domain (TM), two frizzled-like domains (Fz), eight LDL receptor repeats (LDLR), a scavenger receptor domain (SR), and a trypsin-like protease domain with three active site amino acids His (H), Asp (D), and Ser (S). Corin mRNA expression in the atrium and ventricle of a mouse heart at embryonic day 15.5 was detected by in situ hybridization.