NR AVFO
AU Gauczynski,S.; Nikles,D.; 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 acts as a receptor for infectious prions and is inhibited by polysulfated glycanes
QU Journal of Infectious Diseases 2006 Sep 1; 194(5): 702-9
PT journal article
AB BACKGROUND: Recently, we showed that the 37-kDa/67-kDa laminin receptor (LRP/LR) acts as the receptor of the cellular prion protein. METHODS: For the present study, we investigated the binding of the murine scrapie prion protein (moPrP27-30) to baby hamster kidney (BHK) cells, using the Semliki Forest virus system. RESULTS: The enhanced binding of moPrP27-30 to BHK cells expressing moLRP::FLAG was inhibited by the LRP/LR-specific antibody W3, which suggests that LRP/LR acts as a receptor for the scrapie form of the prion protein, PrPsc. This finding was confirmed by a parallel study that showed that bovine prions are internalized by human enterocytes via LRP/LR. The heparan sulfate mimetics HM5004 and HM2602 reduced PrP27-30 binding to moLRP-expressing cells to approximately 30% and approximately 20%, respectively, at a concentration of 10 microg/mL, whereas pentosan polysulfate (SP54) and phycarin sulfate (PS3) both reduced the binding to approximately 40% at a concentration of 100 microg/mL. CONCLUSIONS: We suggest that the inhibition reported elsewhere of PrPsc synthesis and the incubation times prolonged in rodent models by these sulfated glycans are due to the inhibition of the LRP/LR-dependent binding of prions to the target cells.
MH Animals; Cell Line; Cricetinae; Heparitin Sulfate/*pharmacology; Kidney; Mice; Plasmids; PrPsc Proteins/*metabolism; Prions/drug effects/*physiology; RNA, Viral/genetics; Receptors, Laminin/*physiology; Research Support, Non-U.S. Gov't; Semliki forest virus/drug effects/genetics/physiology
AD Laboratorium für Molekulare Biologie-Genzentrum, Institut für Biochemie der LMU München, Munich, Germany.
SP englisch
PO USA