scholarly journals Calmodulin Binds to the Basolateral Targeting Signal of the Polymeric Immunoglobulin Receptor

1996 ◽  
Vol 271 (3) ◽  
pp. 1336-1342 ◽  
Author(s):  
Steven J. Chapin ◽  
Carlos Enrich ◽  
Benjamin Aroeti ◽  
Richard J. Havel ◽  
Keith E. Mostov
Keyword(s):  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor ◽  
Targeting Signal ◽  
Basolateral Targeting

scholarly journals Mutational and secondary structural analysis of the basolateral sorting signal of the polymeric immunoglobulin receptor.

1993 ◽  
Vol 123 (5) ◽  
pp. 1149-1160 ◽  
Author(s):  
B Aroeti ◽  
P A Kosen ◽  
I D Kuntz ◽  
F E Cohen ◽  
K E Mostov
Keyword(s):  
Polymeric Immunoglobulin Receptor ◽  
Terminal Portion ◽  
Alanine Scanning Mutagenesis ◽  
Beta Turn ◽  
Immunoglobulin Receptor ◽  
Helix Structure ◽  
Targeting Signal ◽  
The Stability ◽  
Basolateral Targeting ◽  
Structure In Solution

The 17-juxtamembrane cytoplasmic residues of the polymeric immunoglobulin receptor contain an autonomous basolateral targeting signal that does not mediate rapid endocytosis (Casanova, J. E., G. Apodaca, and K. E. Mostov. Cell. 66:65-75). Alanine-scanning mutagenesis identifies three residues in this region, His656, Arg657, and Val660, that are most essential for basolateral sorting and two residues, Arg655 and Tyr668, that play a lesser role in this process. Progressive truncations suggested that Ser664 and Ile665 might also play a role in basolateral sorting. However, mutation of these residues to Ala or internal deletions of these residues did not affect basolateral sorting, indicating that these residues are probably not required for basolateral sorting. Two-dimensional NMR spectroscopy of a peptide corresponding to the 17-mer signal indicates that the sequence Arg658-Asn-Val-Asp661 has a propensity to adopt a beta-turn in solution. Residues COOH-terminal to the beta-turn (Arg662 to Arg669) seem to take up a nascent helix structure in solution. Substitution of Val660 with Ala destabilizes the turn, while mutation of Arg657 to Ala does not appear to affect the turn structure. Neither mutation detectably altered the stability of the nascent helix in the COOH-terminal portion of the peptide.

The basolateral sorting signal of the polymeric immunoglobulin receptor contains two functional domains

1996 ◽  
Vol 109 (8) ◽  
pp. 2133-2139
Author(s):  
V. Reich ◽  
K. Mostov ◽  
B. Aroeti
Keyword(s):  
Mdck Cells ◽  
Minor Effect ◽  
Polymeric Immunoglobulin Receptor ◽  
Type I ◽  
Apical Surface ◽  
Alanine Scanning Mutagenesis ◽  
Beta Turn ◽  
Immunoglobulin Receptor ◽  
Sorting Signal ◽  
Basolateral Targeting

Basolateral sorting of the polymeric immunoglobulin receptor (pIgR) expressed in Madin-Darby canine kidney (MDCK) cells is mediated by a 17-residue sorting signal that resides in the cytoplasmic domain. We have recently analyzed the sequence requirements of the signal by alanine scanning mutagenesis. We found that basolateral sorting is mediated primarily by three amino acids: H656, R657 and V660. Individual mutations of each of these residues to Ala caused a substantial decrease in basolateral sorting and a corresponding increase in targeting to the apical surface. Structural analysis of 17-residue peptides corresponding to the signal revealed that V660 is in a beta-turn (probably type I) secondary structure, and its mutation to Ala destabilized the turn. H656 and R657 were not part of the turn and substitution of Arg657 to Ala had no effect on the turn stability. These results suggested that the signal is comprised of two structurally distinct domains: a critical V660 in the context of the beta-turn and an additional two residues (H656 and R657) that are not in the turn and probably are unimportant for its stability. Here we provide evidence suggesting that the two domains are distinguishable not only by their structure but also by their function. Basolateral targeting of pIgR mutants bearing Ala mutations at either 656 or 657 was not affected by treatment with brefeldin A (BFA), while basolateral targeting of pIgR containing an Ala substitution at position 660 was markedly and uniquely stimulated by BFA. Compared to single Ala substitutions, simultaneous mutations of H656 and R657 to Ala caused an additional minor effect on basolateral and apical sorting, whereas double mutations of V660 and either H656 or R657 resulted in a maximal decrease in basolateral targeting and corresponding increase in apical targeting. These results suggest the existence of two domains in the signal. When both domains are destroyed, basolateral targeting is maximally inhibited. The results also imply that V660 mediates basolateral sorting by a different mechanism from H656 and R657. We suggest that V660 and perhaps more generally the beta-turn may interact with BFA-sensitive adaptor complexes.

scholarly journals Rapid internalization of the polymeric immunoglobulin receptor requires phosphorylated serine 726.

1994 ◽  
Vol 269 (22) ◽  
pp. 15676-15682 ◽  
Author(s):  
C.T. Okamoto ◽  
W. Song ◽  
M. Bomsel ◽  
K.E. Mostov
Keyword(s):  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor

scholarly journals Rifaximin as a Potential Treatment for IgA Nephropathy in a Humanized Mice Model

2021 ◽  
Vol 11 (4) ◽  
pp. 309
Author(s):  
Vincenzo Di Leo ◽  
Patrick J. Gleeson ◽  
Fabio Sallustio ◽  
Carine Bounaix ◽  
Jennifer Da Silva ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Serum Levels ◽  
Humanized Mice ◽  
Polymeric Immunoglobulin Receptor ◽  
Oral Antibiotic ◽  
Mice Model ◽  
Immunoglobulin Receptor ◽  
Tnf Α ◽  
Factor Α ◽  
Growth Of Bacteria

IgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Rifaximin (NORMIX®), a non-absorbable oral antibiotic, induces positive modulation of the gut microbiota, favoring the growth of bacteria beneficial to the host. Here, we evaluate the effect of rifaximin on a humanized mice model of IgAN (α1KI-CD89Tg). Methods: The α1KI-CD89Tg mice were treated by the vehicle (olive oil) or rifaximin (NORMIX®). Serum levels of hIgA, hIgA1–sCD89, and mIgG–hIgA1 immune complexes were determined. Glomerular hIgA1 deposit and CD11b+ cells recruitment were revealed using confocal microscopy. Furthermore, the mRNA of the B-Cell Activating Factor (BAFF), polymeric immunoglobulin receptor (pIgR), and Tumor Necrosing Factor-α (TNF-α) in gut samples were detected by qPCR. Results: Rifaximin treatment decreased the urinary protein-to-creatinine ratio, serum levels of hIgA1–sCD89 and mIgG–hIgA1 complexes, hIgA1 glomerular deposition, and CD11b+ cell infiltration. Moreover, rifaximin treatment decreased significantly BAFF, pIgR, and TNF-α mRNA expression. Conclusions: Rifaximin decreased the IgAN symptoms observed in α1KI-CD89Tg mice, suggesting a possible role for it in the treatment of the disease.

scholarly journals Ectodomains 3 and 4 of Human Polymeric Immunoglobulin Receptor (hpIgR) Mediate Invasion ofStreptococcus pneumoniaeinto the Epithelium

2003 ◽  
Vol 279 (8) ◽  
pp. 6296-6304 ◽  
Author(s):  
Christine Elm ◽  
Ranveig Braathen ◽  
Simone Bergmann ◽  
Ronald Frank ◽  
Jean-Pierre Vaerman ◽  
...  
Keyword(s):  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor
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