title: PrPc capping in T cells promotes its association with the lipid raft proteins reggie-1 and reggie-2 and leads to signal transduction.
abstract: 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.
authors.affiliation: Department of Biology; University of Konstanz, 78457 Konstanz, Germany. Claudia.Stuermer@uni-konstanz.de
authors.forename: Claudia A O
authors.initials: CA
authors.lastname: Stuermer
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Langhorst
authors.forename: Marianne F
authors.initials: MF
authors.lastname: Wiechers
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Legler
authors.forename: Sylvia Hannbeck
authors.initials: SH
authors.lastname: Von Hanwehr
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Guse
authors.forename: Helmut
authors.initials: H
authors.lastname: Plattner
mesh_terms: 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*
chemical_list: D008565:Membrane Proteins; D018621:PrPC Proteins; C106354:flotillins