Localization of the mosaic transmembrane serine protease corin to heart myocytes

Corin cDNA encodes an unusual mosaic type II transmembrane serine protease, which possesses, in addition to a trypsin-like serine protease domain, two frizzled domains, eight low-density lipoprotein (LDL) receptor domains, a scavenger receptor domain, as well as an intracellular cytoplasmic domain. In in vitro experiments, recombinant human corin has recently been shown to activate pro-atrial natriuretic peptide (ANP), a cardiac hormone essential for the regulation of blood pressure. Here we report the first characteriz ation of corin protein expression in heart tissue. We generated antibodies to two different peptides derived from unique regions of the corin polypept ide, which detected immunoreactive corin protein of approximately 125-135 k Da in lysates from human heart tissues. Immunostaining of sections of human heart showed corin expression was specifically localized to the cross stri ations of cardiac myocytes, with a pattern of expression consistent with an integral membrane localization. Corin was not detected in sections of skel etal or smooth muscle. Corin has been suggested to be a candidate gene for the rare congenital heart disease, total anomalous pulmonary venous return (TAPVR) as the corin gene colocalizes to the TAPVR locus on human chromosom e 4. However examination of corin protein expression in TAPVR heart tissue did not show evidence of abnormal corin expression. The demonstrated corin protein expression by heart myocytes supports its proposed role as the pro- ANP convertase, and thus a potentially critical mediator of major cardiovas cular diseases including hypertension and congestive heart failure.