Stuermer Claudia A O, Langhorst Matthias F, Wiechers Marianne F, Legler Daniel F, Von Hanwehr Sylvia Hannbeck, Guse Andreas H, Plattner Helmut
Department of Biology; University of Konstanz, 78457 Konstanz, Germany.
FASEB J. 2004 Nov;18(14):1731-3. doi: 10.1096/fj.04-2150fje. Epub 2004 Sep 2.
The cellular prion protein (PrPc) resides in lipid rafts, yet the type of raft and the physiological function of PrPc are unclear. We show here that cross-linking of PrPc with specific antibodies leads to 1) PrPc 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 Ca2+ 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 PrPc together with the reggies into limp-2 positive lysosomes. Thus, PrPc association with reggie rafts triggers distinct transmembrane signal transduction events in T cells that promote the focal concentration of PrPc itself by guiding activated PrPc into preformed reggie caps and then to the recruitment of important interacting signaling molecules.
细胞朊蛋白（PrPc）存在于脂筏中，但其脂筏类型及PrPc的生理功能尚不清楚。我们在此表明，用特异性抗体交联PrPc会导致：1）在Jurkat细胞和人外周血T细胞中PrPc形成帽状结构；2）与细胞内脂筏蛋白reggie-1和reggie-2共同形成帽状结构；3）出现信号转导，表现为丝裂原活化蛋白激酶磷酸化以及细胞内Ca2+浓度升高；4）Thy-1、TCR/CD3、fyn、lck和LAT被募集到帽状结构中，同时伴有局部酪氨酸磷酸化和F-肌动蛋白聚合，随后，PrPc与reggie蛋白一起内化进入limp-2阳性溶酶体。因此，PrPc与reggie脂筏的结合会在T细胞中触发不同的跨膜信号转导事件，通过将活化的PrPc引导至预先形成的reggie帽状结构中，进而促进PrPc自身的局部聚集，随后募集重要的相互作用信号分子。
