NR ATHP
AU Stuermer,C.A.O.; Langhorst,M.; Reuter,A.; Plattner,H.
TI Preformed reggie caps: priming platforms for PrPc capping and signaling
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-21
PT Konferenz-Poster
AB
Reggie-1 and -2 are scaffolding proteins of a specific type of lipid raft/microdomain at the cytoplasmic face of the plasmamembrane, where specific GPI anchored proteins, i.e. PrPc cluster and signal into the cell. In T cells, reggies are concentrated in one aspect of the cell, and represent the "preformed cap". Molecular components relevant for T cell activation accumulate in the cap region and co-cluster with reggie. In fact, PrPc coclusters with reggie caps upon antibody-mediated PrPc crosslinking and elicits a distinct intracellular Ca2+ peak which shows that PrPc capping induces signal transduction (Stuermer et al., 2004). We have now transfected Jurkat T cells with a dominant negative reggie-1 construct. This causes the disappearance of the reggie cap whereupon clustering and capping of molecular components relevant for T cell activation no longer takes places (Langhorst et al., subm.) and so the capping of PrPc after antibody-mediated PrPc crosslinking fails to occur. Instead, PrPc forms small patches distributed widely over the cell. These data indicate that PrPc clustering which is required for PrPc-induced signal transduction in T cells, depends on the reggie scaffold in the preformed reggie cap.
The close association of PrPc and reggies was also observed in the intracellular endocytic pathway: they occur together in the same lysosomes, sorting and recycling compartment. However, the first internalisation steps appear to differ: PrPc in contrast to the reggies is internalized via clathrin-coated pits. Yet, when this clathrin-dependent PrPc internalisation is blocked, reggie remains in caps in association with PrPc and the plasma membrane. Together our data suggest a close association and interaction of PrPc with reggie proteins.
Supported by the TR SFB 11/DFG and MWK (TSE program)
AD Claudia A.O. Stürmer, Matthias Langhorst, Alexander Reuter, Helmut Plattner, University of Konstanz, Germany
SP englisch
PO Deutschland