PrP c capping in T cells promotes its association with the lipid raft proteins reggie‐1 and reggie‐2 and leads to signal transduction

• Published in: The FASEB journal 2004-11, Vol.18 (14), p.1731-1733
• Main Authors: Stuermer, Claudia A. O., Langhorst, Matthias F., Wiechers, Marianne F., Legler, Daniel F., Hanwehr, Sylvia Hannbeck von, Guse, Andreas H., Plattner, Helmut
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.04-2150fje

The cellular prion protein (PrP c ) resides in lipid rafts, yet the type of raft and the physiological function of PrP c are unclear. We show here that cross‐linking of PrP c with specific antibodies leads to 1) PrP c capping in Jurkat and human peripheral blood T cells; 2) to cocapping with the intracellular lipid raft proteins reggie‐1 and reggie‐2; 3) to signal transduction as seen by MAP kinase phosphorylation and an elevation of the intracellular Ca 2+ concentration; 4) to the recruitment of Thy‐1, TCR/CD3, fyn, lck and LAT into the cap along with local tyrosine phosphorylation and F‐actin polymerization, and later, internalization of PrP c together with the reggies into limp‐2 positive lysosomes. Thus, PrP c association with reggie rafts triggers distinct transmembrane signal transduction events in T cells that promote the focal concentration of PrP c itself by guiding activated PrP c into preformed reggie caps and then to the recruitment of important interacting signaling molecules.