Disease relevance of ASGR1

• pH-sensitive liposomes composed of dioleoylphosphatidylethanolamine and cholesterol hemisuccinate (3:2 mol/mol) bearing the N-acetylglucosamine derivative of bovine serum albumin (N-Ac-BSA) were applied for receptor-mediated delivery in chicken hepatoma (LMH) cells expressing the N-Ac-BSA-binding asialoglycoprotein receptor [1].

High impact information on ASGR1

• Adaptor binding was partially inhibited by soluble peptides representing the cytoplasmic domains of the asialoglycoprotein receptor and the polymeric immunoglobulin receptor [2].
• The immunoisolated membranes are also enriched in the other MPR, as well as in the asialoglycoprotein receptor [3].
• Removal of sulfate from bLH oligosaccharides and sialic acid from bLH/CHO oligosaccharides results in rapid clearance from the circulation by the hepatocyte asialoglycoprotein receptor [4].
• Thus sulfate, like sialic acid, prevents clearance from the circulation by the asialoglycoprotein receptor [4].
• The asialoglycoprotein-receptor (ASGP-R) located on liver parenchymal cells was originally identified and characterized on the basis of its ability to bind glycoproteins bearing terminal galactose (Gal) or N-acetylgalactosamine (GalNAc); however, endogenous ligands for the ASGP-R have not to date been definitively identified [5].

Biological context of ASGR1

• CONCLUSIONS: By optimizing lipid composition and charge ratio, galactosylated liposome/DNA complexes allow superior in vivo gene transfection in the liver via asialoglycoprotein receptor-mediated endocytosis [6].
• Cells expressing CHL or cells expressing a hybrid receptor that contains the cytoplasmic tail of the asialoglycoprotein receptor display high-efficiency endocytosis of N-acetylglucosamine-conjugated bovine serum albumin in experiments designed to measure an initial internalization step, as well as in studies of continuous uptake and degradation [7].

Anatomical context of ASGR1

• The human asialoglycoprotein receptor expressed by the HepG2 cell line is composed of the two homologous polypeptides H1 and H2 [8].
• The receptor on thyroid membranes for asialothyroglobulin is similar to the asialoglycoprotein receptor on liver membranes (Morell, A.G., Gregoriadis, G., Scheinberg, I.H., Hickman, J., and Ashwell, G. (1971) J. Biol. Chem. 246, 1461-1467) in that sialic acid on the receptor is critical for receptor expression [9].
• The endosome-lysosome transfer of in vivo internalized insulin and glucagon has been studied in a rat liver cell-free system and compared to that of galactosylated bovine serum albumin (GalBSA), a ligand of the asialoglycoprotein receptor [10].
• Normal mice showed 70% of the radioactivity in the hepatocyte, whereas the homozygous ASGPR-deficient mouse had equal activity in the hepatocyte and the hepatic endothelial cell [11].

Associations of ASGR1 with chemical compounds

• Biotin-dependent expression of the asialoglycoprotein receptor in HepG2 [12].
• Addition to dialyzed FBS (dFBS) of 10(-7) M biotin or biocytin (Mr 372) permitted full expression of AsGR by HepG2 [12].
• Resolution of the mRNAs by sucrose gradient centrifugation suggests that cGMP-mediated posttranscriptional regulation of ASGR expression was due to a shift of both H1 and H2 mRNAs from the ribonucleoprotein fraction into a translationally active membrane-associated polysomal pool [8].
• Transblot analysis of HepG2 cell lysates indicated that the progressive loss in the steady-state level of asialoglycoprotein receptor (ASGR) when cells were maintained in medium supplemented with dialyzed fetal bovine serum was reversed by the addition of cell-permeant 8-bromo-cGMP [8].
• The radiolabeled glycoprotein had complete liver uptake in both normal and ASGPR-deficient mice [11].

Analytical, diagnostic and therapeutic context of ASGR1

• Estimates of the steady-state levels of H1- and H2-related mRNA by Northern blot analysis indicated that the reduction of ASGR was not the result of a concomitant reduction in gene transcript number [8].
• Affinity chromatography of FBS on streptavidin-Sepharose abolished its ability to support AsGR production [12].
• Sera from several species, which do not support AsGR production by HepG2, contain less than 10% biotin found in FBS as determined by direct enzyme-linked immunosorbent assay [12].

References