Regulation of the polymeric immunoglobulin receptor by water intake and vasopressin in the rat kidney

1998 ◽  
Vol 274 (5) ◽  
pp. F966-F977 ◽  
Author(s):  
James C. Rice ◽  
Jeff S. Spence ◽  
Judit Megyesi ◽  
Robert L. Safirstein ◽  
Randall M. Goldblum
Keyword(s):  
Water Intake ◽  
Water Deprivation ◽  
Rat Kidney ◽  
Fold Increase ◽  
Secretory Component ◽  
Hydration Status ◽  
Polymeric Immunoglobulin Receptor ◽  
Apical Surface ◽  
Immunoglobulin Receptor ◽  
Amino Terminal

The polymeric immunoglobulin receptor (pIgR) transports polymeric immunoglobulins (IgA) from the basolateral to the apical surface of epithelial cells. At the apical surface, its amino-terminal domain, termed secretory component (SC), is proteolytically cleaved and released either unbound (free SC) or bound to IgA. We examined the effects of changes in water balance and vasopressin on the production and secretion of the pIgR in the rat kidney in vivo. Water deprivation induced a 2.7-fold increase in the pIgR mRNA and a 2.2-fold increase in intracellular pIgR protein compared with water-loaded animals. Physiological doses of desmopressin reproduced the effects of water deprivation on mRNA and intracellular protein levels, suggesting that pIgR expression may be regulated by a vasopressin-coupled mechanism. Secretion of free SC and secretory IgA in the urine, however, correlated directly with water intake and urine flow. These results suggest that hydration status and vasopressin may affect the mucosal immunity of the kidney by regulating at different steps the epithelial cell production and secretion of the polymeric immunoglobulin transporter/secretory component.

Opposite sorting and transcytosis of the polymeric immunoglobulin receptor in transfected endothelial and epithelial cells

1998 ◽  
Vol 111 (9) ◽  
pp. 1197-1206
Author(s):  
T. Su ◽  
K.K. Stanley
Keyword(s):  
Endothelial Cells ◽  
Steady State ◽  
Epithelial Cells ◽  
Cell Line ◽  
Mdck Cells ◽  
Basolateral Membrane ◽  
Secretory Component ◽  
Polymeric Immunoglobulin Receptor ◽  
Apical Surface ◽  
Immunoglobulin Receptor

We have transfected a polarised endothelial cell line, ECV 304, and an epithelial cell line, MDCK, with a well characterised epithelial protein, the rat polymeric immunoglobulin receptor (pIgR), in order to study the protein sorting and transcytosis in endothelial cells. The expressed protein was normally processed and the steady state distribution between apical and basolateral surfaces was similar in both cell types. MDCK cells, however, showed a marked polarity in the delivery of newly synthesised pIgR to the cell surface, and in the release of secretory component. 88% of newly synthesised pIgR in MDCK cells was first delivered to the basolateral surface and 99% of secretory component was released from the apical surface. In contrast the basolateral targeting signal of pIgR was only partially recognised in endothelial cells, with 63% of the newly synthesised pIgR being first delivered to the basolateral surface. At steady state only 43% of the pIgR was found on the basolateral membrane. The direction of dimeric IgA transcytosis in endothelial cells was from apical to basolateral surfaces, opposite to that in MDCK cells. These data suggest that endothelial cells poorly recognise the targeting signals of proteins from epithelial cells, and that the direction of transcytosis is linked to the biological role of the cells.

scholarly journals Functional expression of the polymeric immunoglobulin receptor from cloned cDNA in fibroblasts.

1986 ◽  
Vol 102 (3) ◽  
pp. 911-919 ◽  
Author(s):  
D L Deitcher ◽  
M R Neutra ◽  
K E Mostov
Keyword(s):  
Transmembrane Protein ◽  
Expression System ◽  
Fibroblast Cell ◽  
Functional Expression ◽  
Secretory Component ◽  
Mouse Fibroblast ◽  
Polymeric Immunoglobulin Receptor ◽  
Apical Surface ◽  
Ligand Complex ◽  
Immunoglobulin Receptor

The polymeric immunoglobulin receptor, a transmembrane protein, is made by a variety of polarized epithelial cells. After synthesis, the receptor is sent to the basolateral surface where it binds polymeric IgA and IgM. The receptor-ligand complex is endocytosed, transported across the cell in vesicles, and re-exocytosed at the apical surface. At some point the receptor is proteolytically cleaved so that its extracellular ligand binding portion (known as secretory component) is severed from the membrane and released together with the polymeric immunoglobulin at the apical surface. We have used a cDNA clone coding for the rabbit receptor and a retroviral expression system to express the receptor in a nonpolarized mouse fibroblast cell line, psi 2, that normally does not synthesize the receptor. The receptor is glycosylated and sent to the cell surface. The cell cleaves the receptor to a group of polypeptides that are released into the medium and co-migrate with authentic rabbit secretory component. Cleavage and release of secretory component do not depend on the presence of ligand. The cells express on their surface 9,600 binding sites for the ligand, dimeric IgA. The ligand can be rapidly endocytosed and then re-exocytosed, all within approximately 10 min. Very little ligand is degraded. At least some of the ligand that is released from the cells is bound to secretory component. The results presented indicate that we have established a powerful new system for analyzing the complex steps in the transport of poly-Ig and the general problem of membrane protein sorting.

P0724ASSOCIATIONS OF URINARY POLYMERIC IMMUNOGLOBULIN RECEPTOR PEPTIDES IN THE CONTEXT OF CARDIO-RENAL SYNDROM

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tianlin He ◽  
Justyna Siwy ◽  
Jochen Metzger ◽  
William Mullen ◽  
Harald Mischak ◽  
...  
Keyword(s):  
Secretory Component ◽  
Immune Defense ◽  
Large Cohort ◽  
Polymeric Immunoglobulin Receptor ◽  
Apical Surface ◽  
Peptide Cleavage ◽  
Immunoglobulin Receptor ◽  
Proteome Database ◽  
Artery Disease ◽  
Urinary Peptide

Abstract Background and Aims The polymeric immunoglobulin receptor (pIgR) which transports immunoglobulins from the basolateral to the apical surface of epithelial cells was recently shown to be associated with kidney dysfunction. The immune defense is initiated at the apical surface where the N-terminal domain of pIgR, termed secretory component (SC), is proteolytically cleaved and released either unbound (free SC) or bound to immunoglobulins. The aim of our study was to show the association of pIgR peptides with the cardio-renal syndrome in a large cohort and to get information on how the SC will be released. Method We investigated urinary peptides of 2707 individuals available in the Human Urine Proteome Database using capillary electrophoresis coupled to mass spectrometry. Results The mean abundance of 23 different pIgR peptides correlates negatively with the estimated glomerular filtration rate (eGFR, r=-0.314, p<0.0001). Furthermore, pIgR peptides are significantly increased in coronary artery disease after adjustment for eGFR. We further predicted the proteases involved in urinary peptide generation using the Proteasix tool. Peptide cleavage site analysis suggests that several, and not one, proteases are involved in the generation of the SC. Conclusion In this large cohort, we could demonstrate that pIgR is associated with the cardio-renal syndrome and provide more detailed insights on how pIgR can be potentially cleaved to release the SC.

scholarly journals Targeting Mucosal Sites by Polymeric Immunoglobulin Receptor-directed Peptides

2002 ◽  
Vol 196 (4) ◽  
pp. 551-555 ◽  
Author(s):  
Kendra D. White ◽  
J. Donald Capra
Keyword(s):  
Epithelial Cells ◽  
Fluorescent Protein ◽  
Secretory Component ◽  
In Vivo Studies ◽  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor ◽  
Potential Binding Site ◽  
Green Fluorescent

Polymeric immunoglobulins provide first line humoral defense at mucosal surfaces to which they are specifically transported by the polymeric immunoglobulin receptor (pIgR) on mucosal and glandular epithelial cells. Previous studies from our laboratory suggested that amino acids 402–410 of the Cα3 domain of dimeric IgA (dIgA) represented a potential binding site for the pIgR. Here by binding human secretory component to overlapping decapeptides of Cα3, we confirm these residues and also uncover an additional site. Furthermore, we show that the Cα3 motif appears to be sufficient to direct transport of green fluorescent protein through the pIgR-specific cellular transcytosis system. An alternative approach identified phage peptides, selected from a library by the in vitro Madin Darby Canine Kidney transcytosis assay, for pIgR-mediated transport through epithelial cells. Some transcytosis-selected peptides map to the same 402–410 pIgR-binding Cα3 site. Further in vivo studies document that at least one of these peptides is transported in a rat model measuring hepatic bile transport. In addition to identifying small peptides that are both bound and transported by the pIgR, this study provides evidence that the pIgR-mediated mucosal secretion system may represent a means of targeting small molecule therapeutics and genes to mucosal epithelial cells.

scholarly journals Human free secretory component is composed of the first 585 amino acid residues of the polymeric immunoglobulin receptor

FEBS Letters ◽  
1997 ◽  
Vol 410 (2-3) ◽  
pp. 443-446 ◽  
Author(s):  
Graham J Hughes ◽  
Séverine Frutiger ◽  
Luc-Alain Savoy ◽  
Andrew J Reason ◽  
Howard R Morris ◽  
...  
Keyword(s):  
Amino Acid ◽  
Secretory Component ◽  
Polymeric Immunoglobulin Receptor ◽  
Amino Acid Residues ◽  
Immunoglobulin Receptor

scholarly journals TNF-α Mediated Secretory Component is Positively Regulated by PI3K/AKT/MTOR in CACO-2 Cells

2013 ◽  
Vol 32 (2) ◽  
pp. 116-120 ◽  
Author(s):  
Dongyan Liu ◽  
Si Wang ◽  
Teng Jiang ◽  
Peng Ding
Keyword(s):  
Signaling Pathway ◽  
Real Time Pcr ◽  
Secretory Component ◽  
Secretory Iga ◽  
Polymeric Immunoglobulin Receptor ◽  
Mtor Signaling Pathway ◽  
Quantitative Real Time Pcr ◽  
Immunoglobulin Receptor ◽  
Tnf Α ◽  
Polymeric Immunoglobulins

Summary Background: Secretory component (SC) is the extracellular component of the polymeric immunoglobulin receptor (pIgR) that functions as a receptor for externally secreted polymeric immunoglobulins such as secretory IgA. SC expression is regulated by a signaling pathway involving TNF-a. Methods: Caco-2 cells were cotreated with TNF-a plus either Wortmannin, which inhibits PI3K, or Rapamycin, which inhibits mTOR. The expression of SC and pIgR mRNA were assessed by immunocytochemistry, Western blotting, and Quantitative real-time PCR. Results: Wortmannin and Rapamycin decreased the fraction of cells expressing SC, as well as the total expression of SC protein and pIgR mRNA. Conclusions: TNF-a regulation of SC expression is mediated through a PI3K/AKT/mTOR signaling pathway in Caco-2 cells.

Secretory component: The polymeric immunoglobulin receptor

1985 ◽  
Vol 89 (3) ◽  
pp. 667-682 ◽  
Author(s):  
Dennis J. Ahnen ◽  
William R. Brown ◽  
Thomas M. Kloppel
Keyword(s):  
Secretory Component ◽  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor
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