Corin: A Key Mediator in Sodium Homeostasis, Vascular Remodeling, and Heart Failure

Figure 1. Schematic presentation of corin protein domains. Corin consists of an N-terminal (NH2) cytoplasmic tail, a single-span transmembrane domain (TM), and an extracellular region (indicated) that includes two frizzled domains (Fz1 and Fz2), eight low-density lipoprotein receptor-like repeats (LDLR1-8), a scavenger receptor-like domain (SR), and a trypsin-like serine protease domain at the C-terminus (COOH).

Figure 2. Apical membrane targeting of corin and CD320 in polarized epithelial cells. (A) Corin protein domains are described in the legend of Figure 1. CD320 consists of an N-terminal extracellular region with two LDLR repeats (LDLR1 and LDLR2) and an epidermal growth factor-like domain (EGF), a transmembrane domain (TM), and a C-terminal cytoplasmic tail. A DSSDE amino acid motif (red) is present in the LDLR8 domain in corin and LDLR2 domain in CD320. (B) In non-polarized cells without the Rab11a-mediated apical sorting mechanism, corin and CD320 (red dots) synthesized in the endoplasmic reticulum (ER) are distributed to the entire cell surface (left panel). In polarized epithelial cells with the Rab11a-mediated apical sorting mechanism, the DSSDE motif serves as an apical sorting signal for corin and CD320 expression on the apical, but not basolateral, membrane (right panel).

Figure 3. A proposed role of corin and ANP in the eccrine sweat gland. The eccrine sweat gland in the skin consists of the secretory coil, where initial sweat is produced, and the duct, where ENaC-mediated Na+ reabsorption occurs. Aldosterone promotes ENaC-mediated Na+ reabsorption. In contrast, corin and ANP inhibit ENaC-mediated Na+ reabsorption, thereby increasing Na+ and sweat excretion.

Figure 4. A proposed mechanism of corin and ANP in uterine spiral artery remodeling. In pregnancy, corin is expressed in the uterus to activate ANP, which promotes decidualization of uterine stromal cells and TNF-related apoptosis-inducing ligand (TRAIL) expression. TRAIL released from decidualized stromal cells induces apoptosis (†) in spiral artery smooth muscle cells (SMCs) (1) and cyclophilin B (CyPB) release (2). CyPB, in turn, upregulates TRAIL receptor (TRAILR) expression in spiral artery endothelial cells (ECs) (3), thereby causing TRAIL-mediated apoptosis in ECs (4).