NR AWKY
AU Nikles,D.; Gauczynski,S.; El-Gogo,S.; Papy-Garcia,D.; Rey,C.; Alban,S.; Barritault,D.; Lasmezas,C.I.; Weiss,S.
TI The 37 kDa / 67 kDa laminin receptor: a receptor for infectious prions inhibited by polysulfated glycanes
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-35
PT Konferenz-Poster
AB Recently, we demonstrated that the 37 kDa/67 kDa laminin receptor (LRP/LR) (1) acts as the receptor of the cellular prion protein (2). Here, we analyzed the binding of the infectious mouse scrapie prion protein (moPrP27-30) to BHK cells with the Semliki Forest virus (SFV) system. The enhanced binding of moPrP27-30 to BHK cells hyperexpressing moLRP::FLAG was inhibited by the LRP/LR specific antibody W3 suggesting that LRP/LR acts as a receptor for PrPsc (3). The finding that LRP/LR acts as a receptor for infectious prion proteins was confirmed by a parallel study showing that bovine prions are internalized by human enterocytes, the major cell population of the intestinal epithelium, via LRP/LR (4). The heparan sulfate mimetics HM5004 and HM2602 reduced PrP27-30 binding to moLRP expressing cells at a concentration of 10 µg/ml to approx. 30% and 20%, respectively, whereas pentosan polysulfate (SP54) and phycarin sulfate (PS3) both reduced the binding at a concentration of 100 µg/ml to approx. 40% (3). We suggest that the previously reported inhibition of PrPsc synthesis and prolonged incubation times in rodent models by these polysulfated glycans might be due to the inhibition of the LRP/LR dependent binding of the scrapie prion protein to the target cells (3). (1) Rieger, et al. (1997) Nat. Med., 3, 1383-8, (2) Gauczynski, et al. (2001) EMBO J., 20, 5863-75, (3) Gauczynski, Nikles, et al. (2006) J. Infect. Dis. in press (4) Morel et al. (2005) Am. J. Pathol. 167(4):1033-1042
AD D. Nikles, S. Gauczynski, S. El-Gogo, C. Rey, S. Weiss: Laboratorium für Molekulare Biologie - Genzentrum-Institut für Biochemie der LMU München, Feodor-LynenStr. 25, 81377 München, Germany; D.Papy-Garcia: Laboratoire CRRET/CNRS FRE 2412, Université Paris XII-Val de Marne; S. Alban: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Germany; D. Barritault: OTR3, SAS 4 rue Française, 75001 Paris, France; C.I. Lasmézas: Department of Infectology, Scripps Florida, Jupiter, USA. E-mail: weiss@lmb.uni-muenchen.de
SP englisch
PO Italien