title: Human corin isoforms with different cytoplasmic tails that alter cell surface targeting.
abstract: Corin is a cardiac serine protease that activates natriuretic peptides. It consists of an N-terminal cytoplasmic tail, a transmembrane domain, and an extracellular region with a C-terminal trypsin-like protease domain. The transmembrane domain anchors corin on the surface of cardiomyocytes. To date, the function of the corin cytoplasmic tail remains unknown. By examining the difference between human and mouse corin cytoplasmic tails, analyzing their gene sequences, and verifying mRNA expression in hearts, we show that both human and mouse corin genes have alternative exons encoding different cytoplasmic tails. Human corin isoforms E1 and E1a have 45 and 15 amino acids, respectively, in their cytoplasmic tails. In transfected HEK 293 cells and HL-1 cardiomyocytes, corin isoforms E1 and E1a were expressed at similar levels. Compared with isoform E1a, however, isoform E1 was more active in processing natriuretic peptides. By cell surface labeling, glycosidase digestion, Western blotting, and flow cytometry, we found that corin isoform E1 was activated more readily as a result of more efficient cell surface targeting. By mutagenesis, we identified a DDNN motif in the cytoplasmic tail of isoform E1 (which is absent in isoform E1a) that promotes corin surface targeting in both HEK 293 and HL-1 cells. Our data indicate that the sequence in the cytoplasmic tail plays an important role in corin cell surface targeting and zymogen activation.
authors.affiliation: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou 215123, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Qi
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiang
authors.forename: Mingqing
authors.initials: M
authors.lastname: Zhu
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Wu
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation / Q000502:physiology; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000201:enzymology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004792:Enzyme Precursors; D007527:Isoenzymes; D009124:Muscle Proteins; D012333:RNA, Messenger; C119812:CORIN protein, human; C485617:Corin protein, mouse; D012697:Serine Endopeptidases