ORGN 544 |
Crosslinking of synthetic cell surface receptors by protein ligands triggers endocytosis mediated by lipid rafts
| Siwarutt Boonyarattanakalin, Scott E Martin, and Blake R. Peterson. Department of Chemistry, Pennsylvania State University, 152 Davey Lab, University Park, PA 16802 |
Protein toxins such as shiga toxin and cholera toxin penetrate into cells by binding small molecule-based cell surface receptors localized to cholesterol and sphingolipid-rich lipid raft subdomains of cellular plasma membranes. Molecular recognition between these toxins and their receptors triggers endocytic protein uptake through endogenous membrane trafficking pathways. We report the synthesis of functionally related non-natural cell surface receptors comprising dinitrophenyl (DNP) antigens linked to 3-beta-cholesterylamine as the plasma membrane anchor. These non-natural receptors were directly loaded into plasma membranes of Jurkat lymphocytes to display DNP headgroups from the cell surface. Molecular recognition between these synthetic receptors and added fluorescent anti-DNP antibodies resulted in rapid endocytosis of this protein ligand. The magnitude and rate of protein internalization was highly dependent on the length of linker between the membrane anchor and the DNP headgroup. These effects were correlated with the extent of association of the fluorescent protein with lipid rafts isolated by sucrose density gradient ultracentrifugation of cellular membranes. These results provide evidence that rates of receptor-mediated endocytosis are directly correlated with the efficiency of formation of lipid rafts.  |
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Bioorganic, Molecular Recognition, Asymmetric Reactions and Syntheses
11:00 AM-1:00 PM, Wednesday, September 10, 2003 Javits Convention Center -- Hall 1B/1C, Poster
Sci-Mix
8:00 PM-10:00 PM, Monday, September 8, 2003 Javits Convention Center -- North Pavillion, Sci-Mix
Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003
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