Disease relevance of Asgr1

• It has been demonstrated that the oral administration of ethanol (Lieber-DeCarli liquid diet) to rats results in a decreased expression and content of the asialoglycoprotein receptor (ASGP-R) in the resultant fatty liver [1].
• The rat asialoglycoprotein receptor (ASGP-R) has been expressed in cultured rat hepatoma cells (HTC cells) after transfection with cloned cDNAs [2].
• The findings suggest that the asialoglycoprotein receptor is expressed at high density mainly on cells in zone 1 of the hepatic lobule, and this may have implications for the development of periportal liver damage in chronic active hepatitis [3].
• Use of an asialoglycoprotein receptor-targeted magnetic resonance contrast agent to study changes in receptor biology during liver regeneration and endotoxemia in rats [4].
• In addition, Morris hepatoma 7777 cells, either in culture or growing as a transplantable tumor in vivo, have no detectable ASGP receptor transcripts, while still retaining the ASGP receptor gene [5].

High impact information on Asgr1

• The cholinesterase is found in coated vesicles of presumed endocytic origin following DFP treatment and perfusion for 3 min with galactosylated cholinesterase, a ligand for the asialoglycoprotein receptor [6].
• Using double-label quantitative immunoelectron microscopy on ultrathin cryosections of rat liver, we have compared the endocytotic pathways of the receptors for asialoglycoprotein (ASGP-R), mannose-6-phosphate ligands (MP-R), and polymeric IgA (IgA-R) [7].
• We have used double-label immunoelectron microscopy on ultrathin cryosections of rat liver to identify the site at which the asialoglycoprotein receptor and its ligand dissociate following their common endocytosis [8].
• These observations demonstrate the presence of an asialoglycoprotein receptor on Kupffer cells; therefore, the hepatocyte is not the only cell in the rat liver with D-galactose receptor activity [9].
• Electron microscopic evidence for an asialoglycoprotein receptor on Kupffer cells: localization of lectin-mediated endocytosis [9].

Chemical compound and disease context of Asgr1

• Both the Entamoeba histolytica lectin, a virulence factor for the causative agent of amebiasis, and the mammalian hepatic lectin bind to N-acetylgalactosamine (GalNAc) and galactose (Gal) nonreducing termini on oligosaccharides, with preference for GalNAc [10].
• During the involution of lead nitrate-induced hyperplasia in rat liver (occurring at 5 days after the injection) a significant increase of asialoglycoprotein receptor (ASGP-R) expression on hepatocytes coincided with the massive death by apoptosis of the same cells [11].
• Significant reductions in mRNA levels for liver fatty acid binding protein, albumin, the asialoglycoprotein receptor, connexins 32 and 26, and cytochromes P-450IIB1 and P-450IIE1 were associated with 1% deoxycholic acid feeding [12].

Biological context of Asgr1

• Ninety-six backcross progeny of (BN x WBN/Ila-Ht/Ht) F1 x WBN/Ila-Ht/Ht were typed with microsatellite markers and the gene Ht was mapped on chromosome 10 between Asgr1 and Nos2 within the map distance of 6.2 cM [13].
• Two cDNA clones encoding the predominant form of the asialoglycoprotein receptor from rat liver (the major rat hepatic lectin; RHL-1) were identified by screening a rat liver cDNA library with a mixed oligonucleotide probe 35 nucleotides long [14].
• The kinetics of rat hepatic lectin disappearance were used to estimate a lateral diffusion coefficient greater than 9 x 10(-9) cm2/s at 37 degrees C, suggesting rapid and unimpeded lectin diffusion in the plane of the membrane [15].
• Formation of functional asialoglycoprotein receptor after transfection with cDNAs encoding the receptor proteins [2].
• The number of cell surface binding sites for the asialoglycoprotein receptor was measured with both asialoorosomucoid and ASF as ligands [16].

Anatomical context of Asgr1

• In vitro studies show high uptake of radiolabeled [(153)Sm]-DOTAGal(2) by the human hepatocyte carcinoma cell line Hep G2 containing the asialoglycoprotein receptor (ASGP-R), which is decreased to less than 50% by the presence of its high-affinity ligand asialofetuin (ASF) [17].
• Subsequent translation in a wheat germ lysate produced authentic ASGP receptor which assembled correctly into microsomal membranes [18].
• The plasma membranes of Kupffer cells, endothelial cells, and fat-storing cells were devoid of the asialoglycoprotein receptor [19].
• Cellular distribution of the asialoglycoprotein receptor in rat liver. Implications for hepatic accumulation of desialylated lymphocytes [19].
• Because specific uptake of the asialoglycoprotein haptocorrin has been reported in suckling distal intestine, evidence of the asialoglycoprotein receptor in rat ileum was sought [20].

Associations of Asgr1 with chemical compounds

• Rat liver asialoglycoprotein receptor lacks a cleavable NH2-terminal signal sequence [14].
• The only proteolytic processing occurring in the biosynthesis of RHL-1 is the removal of the NH2-terminal initiator methionine residue [14].
• When ASGP-R protein and mRNA levels were measured in animals infused with ethanol or dextrose in the presence of fish oil (FO) or medium-chain triglyceride as the source of fat, more significant impairments to the ASGP-R were observed in the FO-ethanol group compared with the medium-chain triglyceride-ethanol group [1].
• These results demonstrate that a correlation exists between the progression of alcohol-associated liver injury, as defined by the severity of liver pathology, and an ethanol-induced decline in ASGP-R content [1].
• Using quantitative immunoelectron microscopy with colloidal gold, we found that 2 h and 4 h after cycloheximide administration, the densities of ASGP-R and MP-R in the membranes of the Golgi complex were unaltered compared with control liver [21].

Physical interactions of Asgr1

• These studies suggest that RHL-1 forms a ligand-binding core while RHL-2/3 acts more as an accessory subunit contributing to selective binding of certain oligosaccharide structures [22].
• The rat asialoglycoprotein receptor binds the amino-terminal domain of thyroglobulin [23].
• We conclude that RHL-1 is the Ca(2+)-dependent Lf receptor on hepatocytes and that it binds Lf in a Gal-independent manner [24].

Regulatory relationships of Asgr1

• We studied ASGP-R expression in primary monolayer cultures of rat hepatocytes stimulated to proliferate by the addition of epidermal growth factor and insulin [25].
• Moreover, RHL-1 expressed on the surface of differentiated thyroid cells is able to bind thyroglobulin (Tg), the macromolecular site of synthesis and storage of thyroid hormones [26].

Other interactions of Asgr1

• Neither the distribution of PM and Golgi marker enzymes nor that of the asialoglycoprotein receptor was affected by glucagon treatment [27].
• Growth factor enriched milieu induced a rapid loss of ASGPr with a significant increase of c-Met surface level and a decrease in c-Met protein level [28].
• We previously demonstrated that a heterotypic complex of the two rat asialoglycoprotein receptor subunits was assembled during cell-free translation (Sawyer, J. T., and D. Doyle. 1990. Proc. Natl. Acad. Sci. USA. 87:4854-4858) [29].
• The predominant polypeptide has an apparent molecular weight of 41,500 (RHL-1), while two less abundant species appear to be of higher molecular weight (49,000 (RHL-2) and 54,000 (RHL-3] [30].
• It appears that the three COOH-terminal exons of the asialoglycoprotein receptor gene have been fused into a single exon in the MBP-A gene [31].

Analytical, diagnostic and therapeutic context of Asgr1

• Intracellular site of asialoglycoprotein receptor-ligand uncoupling: double-label immunoelectron microscopy during receptor-mediated endocytosis [8].
• Cryostat sections of perfusion-fixed livers of fasted rats were incubated with peroxidase-labeled antibodies to the rat asialoglycoprotein receptor and were examined by light and electron microscopy [32].
• We used high-resolution immunocytochemistry on ultrathin frozen sections labeled with colloidal gold to study the subcellular distribution of the asialoglycoprotein receptor in rat liver [33].
• In immunoblotting experiments, rat testis galactosyl receptor (RTG-r) is recognized by antiserum raised against the minor ASGP-r species of rat liver (designated rat hepatic lectin-2/3, RHL-2/3) [34].
• The asialoglycoprotein receptor from rat liver was purified by solubilization and affinity chromatography on asialoorosomucoid-Sepharose [35].

References