NR AOSX
AU Gauczynski,S.; El-Gogo,S.; Klankki,E.; Lasmezas,C.I.; Weiss,S.
TI Influence of LRP/LR,PrPc and pentosan polysulfate on the binding and internalization of the mouse scrapie prion protein
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-83
PT Konferenz-Poster
AB
Recently, we identified the PrP interacting 37 kDa/67 kDa laminin receptor (LRP/LR) (1) as the cell surface receptor for the cellular prion protein (PrPc) (2) and HSPGs as co-factors within the PrP-LRP/LR binding complex (3). Furthermore, it has been shown that LRP/LR is required for PrPsc propagation in neuronal cells (4).
Here, we investigated binding and internalization of the proteinase K-digested mouse scrapie prion protein (moPrP27-30) on mammalian cells via the Semliki-Forest-Virus (SFV) system. Enhanced binding of moPrP27-30 to BHK cells was observed when LRP::FLAG was overexpressed to the cell surface and LRP/LR specific antibodies totally blocked the binding reaction suggesting that the 37 kDa/67 kDa laminin receptor might act as a receptor for PrPsc. Expression of recombinant mouse PrP to the cell surface also increased the binding of moPrP27-30 deducing that PrPc might contribute to the cell binding of its infectious counterpart. Internalization studies employing trypsin treatments suggest that moPrP27-30 becomes internalized LRP/LR and PrPc dependently.
Polyanions such as pentosan polysulfate (SP54) have a prophylactic potential in TSEs. Here, we show the inhibititoy effect of SP54 on the binding of moPrP27-30 to LRP::FLAG overexpressing BHK cells suggesting that this substance might interfere with scrapie prion propagation by blocking the moPrP27-30 / 37 kDa/67 kDa LRP/LR interaction on the cell surface.
1. Rieger, R., Edenhofer, F., Lasmezas, C.I. and Weiss, S. (1997) Nat Med, 3, 1383-8.
2. Gauczynski, S., Peyrin, M., Haïk, S., Leucht, C., Hundt, C., Rieger, R., Krasemann, S., Deslys,
J.-P., Dormont, D., Lasmézas, C.I. and Weiss, S. (2001) EMBO J, 20, 5863-5875.
3. Hundt, C., Peyrin, J.-M., Haïk, S., Gauczynski, S., Leucht, C., Riley, M.-L., Rieger, R., Deslys, J.-P.,
Dormont, D., Lasmézas, C.I. and Weiss, S. (2001) EMBO J, 20, 5876-5886.
4. Leucht, C., Simoneau, S., Rey, C., Vana, K., Rieger, R., Lasmezas, C. I., and Weiss, S. (2003) EMBO Rep 4,
290-295
AD S. Gauczynski, S. El-Gogo, E. Klankki, S. Weiss, Laboratorium für Molekulare Biologie-Genzentrum-Institut für Biochemie der LMU München, Germany; C.I. Lasmézas, CEA Laboratory for Prion Pathogenesis, Service de Neurovirologie, DRM/DSV, France
SP englisch
PO Deutschland