Modulation of asialoglycoprotein receptor expression in liver by the endocytic compartment.

CARLOS ENRICH* and W. HOWARD EVANSt * 1)epririimwio t k Hiologiti C ’cdiilrir y Aririrorriiti f’rimlo~ic~ri, Fuciil~ritl rle Mctlic~itiri, Uriirier:sitlurl dij Hurc~clorin, A 11. I)irigotitil s l t i , O ~ ~ O ~ ~ S H t i r c ~ c ~ l o r i r i , S$tii i t i r id t Lahornton of’ I’rortJiri .Striicriire, Nririoiiiil Iri.stitiire j b r Mediciil Hesearch, ,l!iN Ifill, Lotitlori N W7 IAA, U. K . Receptors on animal cell surfaces regulate the uptake o f a large variety o f ligands. including peptide hormones. growth factors. adrenergic agonists and antagonists, metabolic carriers. e.g. transferrin. drugs a s well as toxins [ 11. Many viruses also enter cells by exploiting receptor-mediated endocytic pathways. I t is assumed that endocytic processes, involving membrane recycling, degradation. and additionally in epithelial cells. transcytosis. control the expression of cell surface receptors [ 21. T h e cndocytic compartment is crucially involved in the regulation o f intracellular membrane traffic. However. the possibility can be entertained that this complex organelle is implicated not only in ’inward sorting‘ o f ligands and receptors, but also in thc ’outward sorting‘ o f receptors and other membrane proteins in concert with other organelles involvcd in regulating membrane traffic, e.g. the trurisGolgi apparatus. In liver, receptors. t o which circulating asialoglycoproteins and lipoproteins bind, illustrate its central role in controlling blood metabolites. T h e asialoglycoprotein receptor controls the uptake and degradation of modified plasma glycoproteins. Since its discovery in the early 1970s, the asialoglycoprotcin receptor o r hepatic lectin has been extensively studied and it has become a paradigm for the study of receptor-mediated endocytosis by the liver iri viin in isolated and perfused livers. in primarily cultured hcpatocytes and more recently in the human hepatoma cell line Hep G2 [ 3-61. T h e asialoglycoprotein receptor in hepatocytes has been found in two diffcrent major locations: at the cell surface (in the sinusoidal and lateral plasma membranes) and intracellularly. mainly in endocytic structures, and the Golgi apparatus [ 71. T h e intracellular pool o f receptors is substantially larger than the one found at the cell surface and this raises questions regarding the functional significance o f intracellular reservoirs o f receptors.