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Receptors for Bacterial Toxins, Page 1 of 2
< Previous page Next page > /docserver/preview/fulltext/10.1128/9781555817893/9781555812454_Chap09-1.gif /docserver/preview/fulltext/10.1128/9781555817893/9781555812454_Chap09-2.gifAbstract:
A review of Shiga toxin receptor, diphtheria toxin (DT) receptor, Pseudomonas exotoxin A (PEA) receptors will illustrate the different ways these molecules are studied and that bacterial toxins have harnessed a variety of processes to enter target cells. Evidence presented by researchers that low-density lipoprotein receptor-related protein (LRP) serves as the receptor for PEA is several-fold. First, both the toxin-binding protein purified from LM cells or mouse liver and LRP have similar mobility on SDS-PAGE and are indistinguishable immunologically. Second, native PEA, but not a mutant toxin defective in its ability to bind to LM cells, binds to purified LRP that is immobilized on polystyrene or on nitrocellulose; the toxin interacts with the 515-kDa heavy chain of LRP on ligand blots, not with the 85-kDa light chain. Third, receptor-associated protein (RAP) both blocks binding of PEA to mouse LM cells and abolishes toxicity. Cells expressing receptors with different-length juxtamembrane domains bind DT normally; however, they exhibit reduced sensitivity to DT when compared to wild-type cells. The three receptors have functions essential to the normal physiologic properties of mammalian cells. Nevertheless, they represent molecules usurped by different bacterial toxins as the first step in the intoxication process. Cells lacking functional cell surface receptor are resistant to the toxin, expression of receptor correlates with the tissue specificity of toxin damage, and this in turn correlates with the disease symptoms seen in animal models and in patients.