PrPc capping in T cells promotes its association with the lipid raft proteins reggie-1 and reggie-2 and leads to signal transduction.
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.
Stuermer
Claudia A O
CA
Department of Biology; University of Konstanz, 78457 Konstanz, Germany. Claudia.Stuermer@uni-konstanz.de
Langhorst
Matthias F
MF
Wiechers
Marianne F
MF
Legler
Daniel F
DF
Von Hanwehr
Sylvia Hannbeck
SH
Guse
Andreas H
AH
Plattner
Helmut
H
D020013:Calcium Signaling; D002478:Cells, Cultured; D006801:Humans; D007152:Immunologic Capping; D019169:Jurkat Cells; D008247:Lysosomes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D018621:PrPC Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*
D008565:Membrane Proteins; D018621:PrPC Proteins; C106354:flotillins