Function and regulation of corin in physiology and disease

2020 ◽  
Vol 48 (5) ◽  
pp. 1905-1916
Author(s):  
Ningzheng Dong ◽  
Yayan Niu ◽  
Yue Chen ◽  
Shijin Sun ◽  
Qingyu Wu
Keyword(s):  
Cell Surface ◽  
Current Knowledge ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Electrolyte Balance ◽  
Zymogen Activation ◽  
Cardiac Tissues ◽  
Increased Risk ◽  
Transmembrane Serine Protease ◽  
And Function

Atrial natriuretic peptide (ANP) is of major importance in the maintenance of electrolyte balance and normal blood pressure. Reduced plasma ANP levels are associated with the increased risk of cardiovascular disease. Corin is a type II transmembrane serine protease that converts the ANP precursor to mature ANP. Corin deficiency prevents ANP generation and alters electrolyte and body fluid homeostasis. Corin is synthesized as a zymogen that is proteolytically activated on the cell surface. Factors that disrupt corin folding, intracellular trafficking, cell surface expression, and zymogen activation are expected to impair corin function. To date, CORIN variants that reduce corin activity have been identified in hypertensive patients. In addition to the heart, corin expression has been detected in non-cardiac tissues, where corin and ANP participate in diverse physiological processes. In this review, we summarize the current knowledge in corin biosynthesis and post-translational modifications. We also discuss tissue-specific corin expression and function in physiology and disease.

scholarly journals Cell Surface Expression and Function of the Macromolecular C1 Complex on the Surface of Human Monocytes

2012 ◽  
Vol 3 ◽  
Author(s):  
Kinga K. Hosszu ◽  
Alisa Valentino ◽  
Yan Ji ◽  
Mara Matkovic ◽  
Lina Pednekar ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Human Monocytes ◽  
And Function

scholarly journals Genetic Variations in the Human G Protein-coupled Receptor Class C, Group 6, Member A (GPRC6A) Control Cell Surface Expression and Function

2016 ◽  
Vol 292 (4) ◽  
pp. 1524-1534 ◽  
Author(s):  
Stine Jørgensen ◽  
Christian Theil Have ◽  
Christina Rye Underwood ◽  
Lars Dan Johansen ◽  
Petrine Wellendorph ◽  
...  
Keyword(s):  
Cell Surface ◽  
G Protein ◽  
Control Cell ◽  
Surface Expression ◽  
Genetic Variations ◽  
Cell Surface Expression ◽  
G Protein Coupled Receptor ◽  
Group 6 ◽  
And Function ◽  
G Protein Coupled

scholarly journals C-terminal region regulates the functional expression of human noradrenaline transporter splice variants

2006 ◽  
Vol 401 (1) ◽  
pp. 185-195 ◽  
Author(s):  
Chiharu Sogawa ◽  
Kei Kumagai ◽  
Norio Sogawa ◽  
Katsuya Morita ◽  
Toshihiro Dohi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Surface ◽  
Splice Variants ◽  
Functional Expression ◽  
Surface Expression ◽  
Terminal Region ◽  
Site Directed Mutagenesis ◽  
Cell Surface Expression ◽  
C Terminus ◽  
And Function

The NET [noradrenaline (norepinephrine) transporter], an Na+/Cl−-dependent neurotransmitter transporter, has several isoforms produced by alternative splicing in the C-terminal region, each differing in expression and function. We characterized the two major isoforms of human NET, hNET1, which has seven C-terminal amino acids encoded by exon 15, and hNET2, which has 18 amino acids encoded by exon 16, by site-directed mutagenesis in combination with NE (noradrenaline) uptake assays and cell surface biotinylation. Mutants lacking one third or more of the 24 amino acids encoded by exon 14 exhibited neither cell surface expression nor NE uptake activity, with the exception of the mutant lacking the last eight amino acids of hNET2, whose expression and uptake resembled that of the WT (wild-type). A triple alanine replacement of a candidate motif (ENE) in this region mimicked the influences of the truncation. Deletion of either the last three or another four amino acids of the C-terminus encoded by exon 15 in hNET1 reduced the cell surface expression and NE uptake, whereas deletion of all seven residues reduced the transport activity but did not affect the cell surface expression. Replacement of RRR, an endoplasmic reticulum retention motif, by alanine residues in the C-terminus of hNET2 resulted in a similar expression and function compared with the WT, while partly recovering the effects of the mutation of ENE. These findings suggest that in addition to the function of the C-terminus, the common proximal region encoded by exon 14 regulates the functional expression of splice variants, such as hNET1 and hNET2.

scholarly journals Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants

2000 ◽  
Vol 105 (7) ◽  
pp. 887-895 ◽  
Author(s):  
Jean-Pierre Morello ◽  
Ali Salahpour ◽  
André Laperrière ◽  
Virginie Bernier ◽  
Marie-Françoise Arthus ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Vasopressin Receptor ◽  
Pharmacological Chaperones ◽  
V2 Vasopressin Receptor ◽  
And Function

scholarly journals Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel

2008 ◽  
Vol 294 (5) ◽  
pp. F1157-F1165 ◽  
Author(s):  
Nandita S. Raikwar ◽  
Christie P. Thomas
Keyword(s):  
Cell Surface ◽  
Sodium Channel ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Membrane Expression ◽  
Ww Domains ◽  
Ubiquitin Proteasome ◽  
And Function

We previously reported the existence of multiple isoforms of human Nedd4-2 ( Am J Physiol Renal Physiol 285: F916–F929, 2003). When overexpressed in M-1 collecting duct epithelia, full-length Nedd4-2 (Nedd4-2), Nedd4-2 lacking the NH2-terminal C2 domain (Nedd4-2ΔC2), and Nedd4-2 lacking WW domains 2 and 3 (Nedd4-2ΔWW2,3) variably reduce benzamil-sensitive Na+ transport. We investigated the effect of each of the Nedd4-2 isoforms on cell surface expression and ubiquitination of ENaC subunits. We find that αENaC when transfected alone or with β and γENaC is expressed at the cell surface and this membrane expression is variably reduced by coexpression with each of the Nedd4-2 isoforms. Nedd4-2 reduces the half-life of ENaC subunits and enhances the ubiquitination of α, β, and γENaC subunits when expressed alone or together suggesting that each subunit is a target for Nedd4-2-mediated ubiquitination. As has been reported recently, we confirm that the surface-expressed pool of ENaC is multi-ubiquitinated. Inhibitors of the proteasome increase ubiquitination of ENaC subunits and stimulate Na+ transport in M-1 cells consistent with a role for the ubiquitin-proteasome pathway in regulating Na+ transport in the collecting duct.

scholarly journals Molecular pathogenesis of human CD59 deficiency

2018 ◽  
Vol 4 (6) ◽  
pp. e280 ◽  
Author(s):  
Netanel Karbian ◽  
Yael Eshed-Eisenbach ◽  
Adi Tabib ◽  
Hila Hoizman ◽  
B. Paul Morgan ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Surface ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Membrane Attack Complex ◽  
Surface Expression ◽  
Surface Proteins ◽  
Cell Surface Expression ◽  
Congenital Deficiency ◽  
Recurrent Strokes ◽  
And Function

ObjectiveTo characterize all 4 mutations described for CD59 congenital deficiency.MethodsThe 4 mutations, p.Cys64Tyr, p.Asp24Val, p.Asp24Valfs*, and p.Ala16Alafs*, were described in 13 individuals with CD59 malfunction. All 13 presented with recurrent Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy, recurrent strokes, and chronic hemolysis. Here, we track the molecular consequences of the 4 mutations and their effects on CD59 expression, localization, glycosylation, degradation, secretion, and function. Mutants were cloned and inserted into plasmids to analyze their expression, localization, and functionality.ResultsImmunolabeling of myc-tagged wild-type (WT) and mutant CD59 proteins revealed cell surface expression of p.Cys64Tyr and p.Asp24Val detected with the myc antibody, but no labeling by anti-CD59 antibodies. In contrast, frameshift mutants p.Asp24Valfs* and p.Ala16Alafs* were detected only intracellularly and did not reach the cell surface. Western blot analysis showed normal glycosylation but mutant-specific secretion patterns. All mutants significantly increased MAC-dependent cell lysis compared with WT. In contrast to CD59 knockout mice previously used to characterize phenotypic effects of CD59 perturbation, all 4 hCD59 mutations generate CD59 proteins that are expressed and may function intracellularly (4) or on the cell membrane (2). None of the 4 CD59 mutants are detected by known anti-CD59 antibodies, including the 2 variants present on the cell membrane. None of the 4 inhibits membrane attack complex (MAC) formation.ConclusionsAll 4 mutants generate nonfunctional CD59, 2 are expressed as cell surface proteins that may function in non–MAC-related interactions and 2 are expressed only intracellularly. Distinct secretion of soluble CD59 may have also a role in disease pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document