title: A novel cytoplasmic tail motif regulates mouse corin expression on the cell surface.
abstract: Type II transmembrane serine proteases (TTSPs) are important in many biological processes. Cell surface expression is critical for TTSP activation and function. To date, the mechanism underlying TTSP cell surface expression is poorly understood. Corin is a TTSP and acts as the pro-atrial natriuretic peptide convertase that is essential for sodium homeostasis and normal blood pressure. In this study, we investigated how cytoplasmic tail sequences may regulate corin expression and activation on the cell surface. By site-directed mutagenesis, we made mouse corin proteins with truncations or point-mutations in the cytoplasmic tail. We expressed the mutants in transfected HEK293 cells and analyzed corin cell surface expression and activation by Western blotting and flow cytometry. We found that corin truncation mutants lacking a Lys-Phe-Gln sequence at residues 71-73 had higher levels of cell surface expression and activation compared with that in wild-type corin. When Lys-71, Phe-72 and Gln-73 residues were mutated together, but not individually, in corin with the full-length cytoplasmic tail, increased levels of cell surface expression and zymogen activation were also observed. These results indicate that residues Lys-71, Phe-72 and Gln-73 serve as a novel retention motif in the intracellular pathway to regulate corin cell surface expression and activation.
authors.affiliation: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Ningzheng
authors.initials: N
authors.lastname: Dong
authors.affiliation: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Qi
authors.affiliation: Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Molecular Cardiology, Cleveland Clinic, Cleveland, OH, United States. Electronic address: wuq@ccf.org.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Wu
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015870:Gene Expression; D005998:Glycine / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D011994:Recombinant Proteins; D010649:Phenylalanine; C119812:CORIN protein, human; C485617:Corin protein, mouse; D012697:Serine Endopeptidases; C028736:zymogen E; D008239:Lysine; D005998:Glycine
keywords: Corin; Cytoplasmic tail; Intracellular trafficking; Natriuretic peptides; Transmembrane proteases