Transcytosis of the polymeric Ig receptor requires phosphorylation of serine 664 in the absence but not the presence of dimeric IgA

Hirt, Robert P.; Hughes, Graham J.; Frutiger, Séverine; Michetti, Pierre; Perregaux, Christine; Poulain‐Godefroy, Odile; Jeanguenat, Nathalie; Neutra, Marian R.; Kraehenbuhl, Jean–Pierre

doi:10.1016/0092-8674(93)90416-n

Cited by 84 publications

(64 citation statements)

References 41 publications

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“…Thus, the correlation between loss of phosphorylation and the lack of MPR46 expression at the cell surface suggests that phosphorylation of serine 56 is required for transport to the plasma membrane. This result is consistent with data on pIgR that have shown that mutation of the serine 726 phosphorylation site reduces the number of receptors at the basolateral surface and subsequently the rate of dimeric IgA transcytosis (Hirt et al, 1993). Additionally, the mutant receptor exists as a monomer, and the authors speculate that serine 726 phosphorylation sorting process.…”

Section: Expression Of Mpr46 Mutants In Mpr-deficient Mouse Fibroblastssupporting

confidence: 81%

“…Two tyrosine-based signals (Y688 and Y734) and the phosphorylation of serine 726 regulate the internalization of pIgR (Okamoto et al, 1992(Okamoto et al, , 1994. Finally, phosphorylation of serine 664 stimulates in the absence of receptor ligands the transcytosis of pIgR (Casanova et al, 1990;Hirt et al, 1993) by inactivation of the basolateral-sorting signal.…”

Section: Introductionmentioning

confidence: 99%

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Serine phosphorylation site of the 46-kDa mannose 6-phosphate receptor is required for transport to the plasma membrane in Madin-Darby canine kidney and mouse fibroblast cells.

Breuer

Körner

Böker

et al. 1997

MBoC

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Up to 4% of the human 46-kDa mannose 6-phosphate receptor (MPR46) expressed in Madin-Darby canine kidney (MDCK) cells are localized at the cell surface. At steady state, the expression of MPR46 on the apical surface of filter-grown MDCK cells is about sixfold lower than on the basolateral surface. The cytoplasmic domain of the MPR46 is phosphorylated on serine 56 at low stoichiometry. By expressing mutant MPR46 we have shown that the MPR46 phosphorylation site is required for delivery to the plasma membrane. In addition, mutant MPR46 expressed in MPR-deficient mouse embryonic fibroblasts were not detected at the cell surface and their ability to sort newly synthesized cathepsin D was not altered. Since the loss of MPR46 phosphorylation correlates with the lack of cell surface expression, phosphorylation of serine 56 may either function as a direct plasma membrane targeting signal or inhibit MPR46 recycling from endosomes to Golgi, resulting in trafficking to the cell surface.

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Section: Expression Of Mpr46 Mutants In Mpr-deficient Mouse Fibroblastssupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Serine phosphorylation site of the 46-kDa mannose 6-phosphate receptor is required for transport to the plasma membrane in Madin-Darby canine kidney and mouse fibroblast cells.

Breuer

Körner

Böker

et al. 1997

MBoC

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“…The signals controlling basolateral targeting, endocytosis and sorting of the pIgR for transcytosis in basolateral endosomes involve tyrosine-containing tight beta turns and phosphorylation sites in the receptor's cytoplasmic tail [4,39].…”

Section: Transport Of Piga Into the Mucosal Secretions By The Pigrmentioning

confidence: 99%

The IgA system: a comparison of structure and function in different species

2006

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-The predominant immunoglobulin isotype on most mucosal surfaces is secretory immunoglobulin A (SIgA), a polypeptide complex comprising two IgA monomers, the connecting J chain, and the secretory component. The molecular stability and strong anti-inflammatory properties make SIgA particularly well suited to provide protective immunity to the vulnerable mucosal surfaces by preventing invasion of inhaled and ingested pathogens. In contrast to SIgA, IgA in serum functions as an inflammatory antibody through interaction with FcαR on immune effector cells. Although IgA appears to share common features and protective functions in different species, significant variations exist within the IgA systems of different species. This review will give an overview of the basic concepts underlying mucosal IgA defence which will focus on the variations present among species in structure, antibody repertoire development, pIgR-mediated transport, colostral IgA content, hepatobiliary transport, and function with particular emphasis on the IgA system of the pig and dog. These interspecies variations emphasise the importance of elucidating and analysing the IgA system within the immune system of the species of interest rather than inferring roles from conclusions made in human and mouse studies.

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“…Ligand binding stimulates transcytosis of the wild-type pIgR, as well as S664D and S664A (8,9). Ligand-dependent stimulation suggests that the pIgR may transduce a signal to the cytoplasm.…”

mentioning

confidence: 99%

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

Chapin

Enrich

Aroeti

et al. 1996

Journal of Biological Chemistry

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We have identified a major calmodulin (CaM)-binding protein in rat liver endosomes using 125 I-CaM overlays from two-dimensional protein blots. Immunostaining of blots demonstrates that this protein is the polymeric immunoglobulin receptor (pIgR). We further investigated the interaction between pIgR and CaM using Madin-Darby canine kidney cells stably expressing cloned wild-type and mutant pIgR. We found that detergent-solubilized pIgR binds to CaM-agarose in a Ca 2؉ -dependent fashion, and binding is inhibited by the addition of excess free CaM or the CaM antagonist W-13 (N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide), suggesting that pIgR binding to CaM is specific. The plasma membrane of polarized epithelial cells is divided into apical and basolateral surfaces, each having a distinct protein and lipid composition. Cells use two pathways to deliver proteins to the correct surface. First, newly made proteins are packaged in the trans-Golgi network (TGN) 1 into vesicles that deliver them directly to either the apical or basolateral surface. Second, proteins can be delivered first to one surface and then endocytosed and transcytosed to the opposite surface. At least in the well polarized Madin-Darby canine kidney (MDCK) cell line, targeting to the basolateral surface generally requires a sorting signal located in the cytoplasmic domain of the protein. For a number of basolateral proteins it has been found that mutations in the cytoplasmic domain prevent TGN to basolateral targeting (1). The first basolateral signal to be identified is the 17-amino acid membrane proximal segment (residues 653-670) of the cytoplasmic domain of the polymeric immunoglobulin receptor (pIgR) (2). This protein is normally delivered from the TGN to the basolateral surface, and then endocytosed and transcytosed to the apical surface. Deletion of most of this 17-residue segment prevents TGN to basolateral delivery. Moreover, this segment can be transplanted to a heterologous reporter molecule, which is then retargeted from the apical to the basolateral surface (2). In at least one other case, the low density lipoprotein receptor, autonomous basolateral sorting signals have been identified (3).The pIgR basolateral targeting signal has been systematically analyzed by alanine scanning mutagenesis (4). Mutation of His-656, Arg-657, or Val-660 to Ala substantially diminishes, but does not eliminate, TGN to basolateral targeting. Mutation of other residues had little or no effect. The structure of a synthetic 17-residue peptide corresponding to this signal has been determined by two-dimensional nuclear magnetic resonance spectroscopy (4). This peptide tends to adopt a putative type 1 ␤-turn, encompassing residues 658 -661, followed by a nascent helical structure. In MDCK cells polarized sorting takes place in both the TGN and after endocytosis. Mutations that diminish TGN to basolateral sorting and increase TGN to apical sorting have a similar effect on sorting in the endocytotic pathway, decreasing recycling to the basolateral surface and...

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Transcytosis of the polymeric Ig receptor requires phosphorylation of serine 664 in the absence but not the presence of dimeric IgA

Cited by 84 publications

References 41 publications

Serine phosphorylation site of the 46-kDa mannose 6-phosphate receptor is required for transport to the plasma membrane in Madin-Darby canine kidney and mouse fibroblast cells.

Serine phosphorylation site of the 46-kDa mannose 6-phosphate receptor is required for transport to the plasma membrane in Madin-Darby canine kidney and mouse fibroblast cells.

The IgA system: a comparison of structure and function in different species

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

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