Distinct Functional Regions of the Human Polymeric Immunoglobulin Receptor

Abstract

The polymeric immunoglobulin receptor (pIgR) is a type I transmembrane protein that is expressed on the surfaces of glandular and intestinal epithelial cells. The extracellular portion of the pIgR is composed of six different domains. Domain 6 is involved in the enzymatic cleavage and release of the pIgR into the intestinal lumen as a free secretory component (fSC). A highly conserved 9-amino acid sequence is present in this region in various species. Although mutations in domain 6 are associated with particular diseases, such as IgA nephropathy and Epstein-Barr virus-related nasopharyngeal cancer, and the glutamic acid residues in the conserved 9-amino acid sequence are expected to be indispensable for the secretion of fSC, the importance of these residues has not been examined. In the present study, we attempted to examine the role of these residues in the enzymatic cleavage of the pIgR. The enzymatic cleavage of the pIgR was not affected by the presence of an alanine to valine substitution at position 580 or glutamine to alanine substitutions at positions 606 and/or 607, or the deletion of the whole 9-amino acid conserved sequence. Intriguingly, the 10 amino acid sequences flanking the N-and C-terminal ends of the conserved 9-amino acid sequence had opposite effects on pIgR cleavage. Namely, the N-terminal and Cterminal sequences enhanced and reduced pIgR cleavage efficiency, respectively. These results indicated that the pIgR can be divided into several functionally distinct regions.

Proteomic pattern of breast milk discriminates obese mothers with infants of delayed weight gain from normal‐weight mothers with infants of normal weight gain

“…In the latter case, it is likely that full‐length pIgR is very rapidly degraded during the first 20–30 min process of breast milk collection. This is corroborated by a recent study that pinpoints pIgR as one of the two human milk proteins that are most affected by enzymatic hydrolysis , albeit some enzymes still remain unidentified .…”

Associations of urinary polymeric immunoglobulin receptor peptides in the context of cardio-renal syndrome

“…First, the vast majority of the identified endogenous peptides are derived from domain 6 of the extracellular region in the pIgR protein (see Fig. 1), as described in the study of Sunagawa et al 17 . Interestingly, the lowest AA number of the identified urinary peptides starts at position 576 of the pIgR protein and not at position 575.…”

“…In a study using a recombinant vaccinia virus-mediated transient expression system, the importance of domain 6 of the pIgR for cleavage of the receptor was demonstrated 19 . A highly conserved 9-amino acid sequence is present in this region in various species 17 . This 9-amino acid sequence FAEEKAVAD ranging from position 605 to position 613 in pIgR is predicted to encode an α-helical region that is critical for pIgR cleavage 17 .…”

“…A highly conserved 9-amino acid sequence is present in this region in various species 17 . This 9-amino acid sequence FAEEKAVAD ranging from position 605 to position 613 in pIgR is predicted to encode an α-helical region that is critical for pIgR cleavage 17 . In our study, we found that 10 of the 24 different urinary peptides include these 9 AAs.…”

Novel Monoclonal Antibodies for Studies of Human and Rhesus Macaque Secretory Component and Human J-Chain

“…Genes and recombinant proteins of J-chain, SC, and IgA antibodies DNA sequences of human J-chain (accession number: P01591) (30) and pIgR of human (accession number: NM_002644) (31) and rhesus macaque (accession number: EHH15602) (31) were obtained from the GenBank. For production of soluble recombinant proteins and use as DNA immunization in mice, genes encoding for human J-chain and human and rhesus free SC (2,32) were codon optimized by converting amino acid sequences to nucleotide sequences using the codon usage of highly expressed human housekeeping genes and de novo synthesized (GenScript).…”