Disease relevance of Pigr

• Here we show that cholestasis induced by bile duct ligation results in the accumulation of transcytotic carriers, identified by the 120 x 10(3) Mr pIgA-R and pIgA, in the pericanalicular cytoplasm of hepatocytes [1].
• The IgA/IgM receptor expressed on a murine B cell lymphoma is poly-Ig receptor [2].
• Caloric deficiency in an experimental system that closely resembles human marasmus results in a decrease in the quantity of the pIgR that is sufficient to account for the low concentration of IgA in the mucous secretions of the intestine [3].
• Considered together with recent evidence pertaining to weanling protein deficiency, these results permit the conclusion that the pIgR is a focal point of the impact exerted by metabolically diverse forms of protein-energy malnutrition on mucosal humoral immunocompetence [3].
• We examined the effects of an ischemic model of acute renal failure (ARF) on the expression of pIgR and the secretion of FSC and S-IgA in the urine [4].

Psychiatry related information on Pigr

• 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 [5].

High impact information on Pigr

• It was concluded that phosphorylation is the signal that directs the pIgR from the endosome into the transcytotic pathway [6].
• When exogenous receptor was expressed in Madin-Darby Canine Kidney (MDCK) cells, it was shown that phosphorylation of pIgR at the serine residue at position 664 is required for efficient transcytosis [6].
• Transcytosis of polymeric immunoglobulin A (pIgA) across epithelial cells is mediated by the polymeric immunoglobulin receptor (pIgR) [7].
• Analysis of p62yes knockout mice revealed a dramatic reduction in the association of tyrosine kinase activity with the pIgR and in transcytosis of pIgA [7].
• Binding of pIgA to pIgR stimulates transcytosis of the pIgA-pIgR complex via a signal transduction pathway that is dependent on a protein tyrosine kinase (PTK) of the SRC family [7].

Biological context of Pigr

• A 43-base-pair complementary DNA sequence homology and triplet repeat motif among putative polymeric immunoglobulin receptor messenger RNAs in regenerating rat liver [8].
• Control and cholestatic hepatocytes trafficked [35S]-labeled serum proteins and the pIgA-R along the secretory pathway with identical kinetics [9].
• In Fisher rats, elements within or beyond the STMS are expressed variably in the 3' untranslated regions (3'UTRs) of two 'Groups' of PIGR-encoded hepatic mRNAs (pIg-R) during liver regeneration [10].
• An unusual S1-nuclease sensitive microsatellite (STMS) has been found in the single copy, rat polymeric immunoglobulin receptor gene (PIGR) terminal exon [10].
• Attenuation of gene expression by a trinucleotide repeat-rich tract from the terminal exon of the rat hepatic polymeric immunoglobulin receptor gene [11].

Anatomical context of Pigr

• Intracellular accumulation of pIgA-R and regulators of transcytotic trafficking in cholestatic rat hepatocytes [9].
• To determine the extent of pIgA-R accumulation, hepatic total microsomes (TM) were prepared from control and cholestatic rats [1].
• Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor [12].
• By immunofluorescence microscopy, pIgR, like the synaptic vesicle protein synaptophysin, accumulates in both the cell body and the neurites [13].
• The polymeric immunoglobulin receptor accumulates in specialized endosomes but not synaptic vesicles within the neurites of transfected neuroendocrine PC12 cells [13].

Associations of Pigr with chemical compounds

• The starting preparation is a Golgi light fraction (GLF) isolated by flotation in a discontinuous sucrose density gradient and processed through immunoisolation on magnetic beads coated with an antibody against the last 11 aa. of the pIgA-R tail [14].
• Finally, the rate of transcytosis of dimeric IgA and its appearance in bile are not affected when disulfide bond formation with polymeric immunoglobulin receptor is inhibited by blocking of free thiol groups on dimeric IgA with iodoacetamide [15].
• The transcellular transport of polymeric immunoglobulins (pIg) across mucosal epithelia is mediated by a membrane glycoprotein known as the polymeric immunoglobulin receptor (pIgR) [16].
• No significant changes were observed in the pIgR mRNA levels of animals treated with progesterone alone or with a combination of estradiol and progesterone [17].
• When ovariectomized rats were treated with estradiol, progesterone, or a combination of the two for 3 days, pIgR mRNA levels were significantly reduced in estradiol-treated animals relative to saline-treated controls [17].

Physical interactions of Pigr

• Interestingly, only in those isolated endosomal fractions, endosomes enriched in transcytotic structures (of livers loaded with IgA), the polymeric immunoglobulin receptor specifically co-immunoprecipitated with cellubrevin [18].

Co-localisations of Pigr

• ClC-5 partially colocalized with the transcytosed polymeric immunoglobulin receptor but was not detectable together with the brush-border-anchored sucrase isomaltase [19].

Other interactions of Pigr

• In conclusion, these data indicate that the secretory and transcytotic pathways remain polarized in cholestatic hepatocytes and suggest that the pIgA-R traffics through postendosomal rab3D-, rab11a-, and syntaxin 2-associated compartments, implicating these proteins in the regulation of transcytosis [9].
• Using a one-step fractionation technique to separate a highly enriched fraction of Golgi-derived membranes from ER and PM, we find that both 5NT and the polymeric IgA receptor (pIgAR) traverse the ER and Golgi apparatus with high efficiency [20].
• Using immunoblot analysis, we found that pIgA-R was released into bile at a rate of 30%/h (700%/day), whereas dipeptidyl peptidase IV and HA4 were released at a rate of 2-3%/day [21].
• RESULTS: Microarray analysis revealed that major alpha-hemoglobin, polymeric immunoglobulin receptor, catalase, and CCAAT/enhancer protein alpha gene expression were down-regulated in livers of MMF-treated rats 10-, 5.5-, 4-, and 5-fold, respectively [22].
• Aging effects on hepatic NADPH cytochrome P450 reductase, CYP2B1&2, and polymeric immunoglobulin receptor mRNAs in male Fischer 344 rats [23].

Analytical, diagnostic and therapeutic context of Pigr

• Bile duct ligation (BDL) impairs basolateral-to-apical transcytosis in hepatocytes, causing accumulation of transcytotic carriers for the polymeric IgA receptor (pIgA-R) and redistribution of secretory component (SC) from bile to blood [9].
• Positive sites for pIgA-R were localized to the pericanalicular cytoplasm of hepatocytes by indirect immunofluorescence on semithin frozen sections in cholestatic hepatocytes [1].
• In addition, cells from old animals showed markedly diminished secretion of secretory component determined by enzyme-linked immunosorbent assay and expression of polymeric immunoglobulin receptor determined by incorporation of 35S-labeled amino acid and fluorography [24].
• By using a rabbit polyclonal antibody against the rat secretory component domain of the pIgR, Western blot analysis demonstrated that the plasma-membrane-bound pIgR levels in hepatocytes from rats aged 19-22 dPP increased 10-fold during this period [25].
• To determine whether or not this increase in membrane-bound pIgR reflected increased pIgR gene expression, we probed Northern blots of total cellular RNA extracted from neonatal rat liver with pIgR cDNA [GORF-1; Banting, G., Brake, B., Braghetta, P., Luzio, J.P. & Stanley, K. K. (1989) FEBS Lett. 254, 177-183] [25].

References