The 37-kDa/67-kDa laminin receptor acts as a receptor for infectious prions and is inhibited by polysulfated glycanes.
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, PrP(Sc). 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 PrP(Sc) 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.
Gauczynski
Sabine
S
Laboratorium fur Molekulare Biologie-Genzentrum, Institut fur Biochemie der LMU Munchen, Munich, Germany.
Nikles
Daphne
D
El-Gogo
Susanne
S
Papy-Garcia
Dulce
D
Rey
Clemence
C
Alban
Susanne
S
Barritault
Denis
D
Lasmezas
Corinne Ida
CI
Weiss
Stefan
S
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006497:Heparan Sulfate / Q000494:pharmacology*; D007668:Kidney; D051379:Mice; D010957:Plasmids; D018620:PrPSc Proteins / Q000378:metabolism*; D011328:Prions / Q000187:drug effects / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics; D017474:Receptors, Laminin / Q000502:physiology*; D012672:Semliki forest virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D006497:Heparan Sulfate; D018620:PrPSc Proteins; D011328:Prions; D012367:RNA, Viral; D017474:Receptors, Laminin