Receptor-mediated uptake

Homof M, de la FM, Hallikainen M, Tammi RH, Urtti A (2008) Low molecular weight hyaluronan shielding of DNA/PEI polyplexes facilitates CD44 receptor mediated uptake in human corneal epithelial cells. J Gene Med 10 70-80... 

Loscalzo (L22) has reported another possible mechanism by which Lp(a) is catabolized, i.e., a non-receptor-mediated uptake by the endothelium. 

Nishikawa, K., Arai, H., and Inoue, K., 1990, Scavenger receptor-mediated uptake and metabohsm of lipid vesicles containing acidic phosphohpids by mouse peritoneal macrophages./. Biol. Chem. 265 5226-5231. 

If bound first by albumin, heme circulates until it is transferred to hemopexin (52). In vitro in the absence of hemopexin, nonspecific cellular uptake of heme by diffusion is facile (55), but as expected, the presence of hemopexin greatly slows uptake (54), since receptor-mediated uptake is necessarily slower and of lower capacity than diffusion-limited uptake. There is currently no evidence that either receptors for albumin or membrane transporters for heme, like those in prokaryotes, are present in the plasma membrane of mammalian cells, although such transport proteins may be present in the membranes of organelles. 

Macromolecules such as polypeptides and proteins are excluded from uptake by diffusion or through pores at the BBB. However, the presence of receptor-mediated uptake and transport into the brain has been found for a number of substances. Specific receptors for insulin and... 

Receptor-mediated uptake mechanisms have also been shown for insuhn, insulin-hke growth factors, and leptin. The fact that macromolecular complexes as large as LDL can un-... 

Methods of traversing the basolateral membrane include uptake systems for organic cations and anions via fadhtated diffusion and/or active transport [1]. Organic anions and cations cross the basolateral membrane via ATP-driven or secondary active processes (H -antiport) [2]. Basolateral uptake processes include the gamma-glutamyl transport system [3] and those for glycoproteins [4]. Certain proteins (insulin, epidermal growth factor (EGF)) are transcytosed across the tubular cells from the blood to the tubular lumen via receptor-mediated uptake [5]. 

An increased rate of metabolic clearance has been observed after removal of sialic acid from human, low-density lipoprotein in vivo.472 Sialic acid controls the receptor-mediated uptake of this lipoprotein by fibroblasts. Removal of sialic acid residues accelerates the rate of internalization of the lipoprotein and, subsequently, the regulation of the metabolism of cellular cholesterol.473... 

Mammalian cells acquire cholesterol either by de novo synthesis from acetyl-coen-zyme A (CoA) or via the low-density lipoprotein (LDL)-receptor-mediated uptake of LDL particles that contain cholesterol esterified with long-chain fatty acids. These LDL cholesterol esters are subsequently hydrolyzed in lysosomes, after which free cholesterol molecules become available for synthesis of membranes, steroid hormones, bile acids, or oxysterols [1]. 

Some people with elevated lipoprotein levels have VLDL that migrates on electrophoresis in the (3 band rather than the pre-(3 band (see Box 2-A). The presence of the (3-VLDL is associated with a high incidence of artery disease,218 which is most likely to develop in persons homozygous for a genetic variant of apolipoprotein E. The problem may arise because apo-E is required for receptor-mediated uptake of VLDL, which interacts both with tissue LDL receptors and with hepatic apo-E receptors. Genes for many of the... 

Receptor-mediated uptake of LDL by human skin fibroblasts. Specific LDL receptors are located in coated regions of the plasma membrane. LDL binding results in uptake by endocytosis and formation of a coated vesicle. This vesicle fuses with a lysosome containing many hydrolytic enzymes that degrade the lipoprotein, releasing cholesterol. 

Perales, J.C., Ferkol, T., Beegen, H., RatnoIF, O.D. and Hanson, R.W. (1994) Gene transfer in vivo sustained expression and regulation of genes introduced into the liver by receptor-mediated uptake. Proc. Natl. Acad. Sci. USA, 91,4086 1090. 

Numerous studies have pointed to an important role for cholesterol during proliferation and progression of cancer (e.g., ref. 612-615). Rapidly dividing cancer cells have two major routes to fulfill their need for cholesterol to form new cell membrane endogenous synthesis of cholesterol and/or receptor-mediated uptake of exogenous LDL particle-associated cholesterol and cholesterol esters (ref. 612,613,615). Each LDL particle contains a cholesterol ester core surrounded by a polar shell of phospholipids (primarily phosphoglycerides), free cholesterol, and apolipoprotein B (ref. 616-618). Once bound to its cell surface receptor, LDL is internalized by receptor-mediated endocytosis and degraded in lysosomes, and the subsequently released cholesterol may be used for membrane synthesis by the tumor (ref. 619). 

Monocyte-macrophages are the only principal cells of the immune system that can synthesize all the eicosanoids. T and B lymphocytes are interesting exceptions to the general rule that all nucleated cells produce eicosanoids. However, in a B lymphoma cell line, there is non-receptor-mediated uptake of LTB4 and 5-HETE. Interaction between lymphocytes and monocyte-macrophages may cause the lymphocytes to release arachidonic acid from their cell membranes. The arachidonic acid is then used by the monocyte-macrophages for eicosanoid synthesis. In addition to these cells, there is evidence for eicosanoid-mediated cell-cell interaction by platelets, erythrocytes, PMNs, and endothelial cells. 

The plasma half-life of LDL is about 2 days, and their primary function is the delivery of cholesterol to the tissues. LDL are taken up into cells by two routes, one that is receptor mediated (and is regulated by the cholesterol requirement of the cell) and one that appears to be nonreceptor mediated (and depends entirely on the extravascular concentrations of LDL). The receptor-mediated uptake occurs by binding of apo-BlOO, which is predominantly present on LDL. Hence these receptors are also known as LDL receptors and have been identified on a variety of cell types. In normal humans, about two thirds of total LDL clearance is mediated by the LDL receptor, and about 80-90% of the receptor-mediated uptake occurs in the liver. However, the relative importance of receptor and nonreceptor-mediated LDL uptake can vary depending on factors including diet and different disease states. 

N. R. Pimstone, R. C. Stadalinik, D. R. Vera, D. P. Hutak, and W. L. Trudeau, Evaluation of hepatocellular function by way of receptor-mediated uptake of a Technetium-99m-labeled asialoglycoprotein analog, Hepatology 20 917-923 (1994). 

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