Modulation of signal transduction through the cellular prion protein is linked to its incorporation in lipid rafts.
Because expressed at a significant level at the membrane of human T cells, we made the hypothesis that the cellular prion protein (PrPc) could behave as a receptor, and be responsible for signal transduction. PrPc engagement by specific antibodies was observed to induce an increase in cytosolic calcium concentration and led to enhanced activity of Src protein tyrosine kinases. Antibodies to CD4 and CD59 did not influence calcium fluxes or signaling. The effect was maximal after the formation of a network involving avidin and biotinylated antibody to PrPc and was inhibited after raft disruption. PrPc localization was not restricted to rafts in resting cells but engagement was a prerequisite for signaling induction, with concomitant PrPc recruitment into rafts. These results suggest a role for PrPc in signaling pathways, and show that lateral redistribution of the protein into rafts is important for subsequent signal transduction.
Hugel
B
B
Institut d'Hématologie et d'Immunologie, Faculté de Médecine, Université Louis Pasteur, 4 rue Kirschleger, 67085 Strasbourg, France. Benedicte.Hugel@hemato-ulp.u-strasbg.fr
Martínez
M C
MC
Kunzelmann
C
C
Blättler
T
T
Aguzzi
A
A
Freyssinet
J-M
JM
D000911:Antibodies, Monoclonal / Q000737:chemistry; D001360:Avidin / Q000494:pharmacology; D015153:Blotting, Western; D015704:CD4 Antigens / Q000096:biosynthesis; D018957:CD59 Antigens / Q000096:biosynthesis; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007476:Ionophores; D021962:Membrane Microdomains / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D011328:Prions / Q000737:chemistry*; D015398:Signal Transduction; D013395:Sucrose / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D018957:CD59 Antigens; D003432:Cross-Linking Reagents; D007476:Ionophores; D011328:Prions; D001360:Avidin; D004533:Egtazic Acid; D013395:Sucrose; D019061:src-Family Kinases; D002118:Calcium