Heparan proteoglycans

In cells containing low amounts of surface heparans, the toxin does not bind well unless soluble heparin is added (Valdizan et al., 1995). Apparently, the heparin-binding site of the toxin receptor covers the binding site for the toxin until heparin is bound. In normal animal cells surface heparan proteoglycans carry out this function. 

There are other glycosaminoglycans. Hyaluronic acid [9004-61-9] occurs both free and in noncovalent association with proteoglycan molecules. Heparin [9005-49-6] and heparan sulfate [39403-40-2] also known as heparitin sulfate [9050-30-0] occur in mast cells and in the aorta, Hver, and lungs. 

Certain proteoglycans (eg, heparan sulfate) are associated with the plasma membrane of cells, with their core proteins acmally spanning that membrane. In it they may act as receptors and may also participate in the mediation of cell growth and cell-cell communication. The attachment of cells to their substramm in cul-mre is mediated at least in part by heparan sulfate. This proteoglycan is also found in the basement membrane of the kidney along with type IV collagen and laminin... 

The intima of the arterial wall contains hyaluronic acid and chondroitin sulfate, dermatan sulfate, and heparan sulfate proteoglycans. Of these proteoglycans, dermatan sulfate binds plasma low-density lipoproteins. In addition, dermatan sulfate appears to be the major GAG synthesized by arterial smooth muscle cells. Because it is these cells that profiferate in atherosclerotic lesions in arteries, dermatan sulfate may play an important role in development of the atherosclerotic plaque. 

Oravecz T, Pall M, Wang J, Roderiquez G, Ditto M, Norcross MA. Regulation of anti-HIV-1 activity of RANTES by heparan sulfate proteoglycans. J Immunol 1997 159(9) 4587 1592. 

Valenzuela-Femandez A, Palanche T, Amara A, et al. Optimal inhibition of X4 HIV isolates by the CXC chemokine stromal cell-derived factor 1 alpha requires interaction with cell surface heparan sulfate proteoglycans. J Biol Chem 2001 276(28) 26550-26558. 

Perrimon, N. and Bernfield, M. (2000), Specificities of heparan sulphate proteoglycans in developmental processes , Nature (London), 404, 725-728. 

Alvarez-Dominguez, C., Vazquez-Boland, J. A., Carrasco-Martin, E., Lopez-Mato, P., and Leyva-Cobain, E. (1997). Host cell heparan sulfate proteoglycans mediate attachment and entry of Listeria monocytongenes, and the listerial surface protein ActA is involved in heparan sulfate receptor recognition. Infect. Immun. 65, 78-88. 

Fleckenstein, J. M., Holland, J. T., and Hasty, D. L. (2002). Interaction of an outer membrane protein of enterotoxigenic Escherichia coli with cell surface heparan sulfate proteoglycans. Infect. Immun. 70,1530-1537. 

Marty C, Meylan C, Schott H, et al. Enhanced heparan sulfate proteoglycan-mediated uptake of cell-penetrating peptide-modified liposomes. Cell Mol Life Sci 2004 61 (14) 1785-1794. 

Type I collagen can interact with various other molecules in the extracellular matrix and on the cell surface. Cell receptors of type I collagen have been identified and include the heterodimeric integrin family receptors, ctl, 0 2, olO, and ol 1, especially o2/3l, the receptor tyrosine kinase discoidin domain receptor (DDR), and the heparan sulfate membrane proteoglycan syndecan family... 

The rationale for this type of contrast agent is to use the endogenous metabolic pathway of lipid metabolism in the liver for the transport of iodinated substances. Chylomicron remnants are naturally occurring lipoproteins in the blood that are responsible for the transport of lipids into the liver. Three different mechanisms for this transport are discussed direct uptake by the low-density lipoprotein receptor transport to the low-density lipoprotein receptor-related protein (LRP) mediated by heparan sulfate proteoglycan (HSPG) or direct HSPG-LRP uptake and direct HSPG uptake. One of the prerequisites for particles to be transported by these mechanisms is a mean diameter of less than 100-300 run. 

Murthy, K. H., et al. (2001). Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans. Cell 104,301-311. 

Stow JL, de Almeida JB, Narula N, Holtzman EJ, Ercolani L, Ausiello DA (1991) A heterotrimeric G protein, G alpha i-3, on Golgi membranes regulates the secretion of a heparan sulfate proteoglycan in LLC-PKl epithelial cells. J Cell Biol 114 1113-1124... 

---