The 37 kDa/67 kDa laminin receptor is required for PrP(Sc) propagation in scrapie-infected neuronal cells.
The accumulation of PrP(Sc) in scrapie-infected neuronal cells has been prevented by three approaches: (i) transfection of ScMNB cells with an antisense laminin receptor precursor (LRP) RNA-expression plasmid, (ii) transfection of ScN2a cells and ScGT1 cells with small interfering RNAs (siRNAs) specific for the LRP mRNA, and (iii) incubation of ScN2a cells with an anti-LRP/LR antibody. LRP antisense RNA and LRP siRNAs reduced LRP/LR expression and inhibited the accumulation of PrP(Sc) in these cells. The treatments also reduced PrP(c) levels. The anti-LRP/LR antibody, W3, abolished PrP(Sc) accumulation and reduced PrP(c) levels after seven days of incubation. Cells remained free of PrP(Sc) after being cultured for 14 additional days without the antibody, whereas the PrP(c) level was restored. Our results demonstrate the necessity of the laminin receptor (LRP/LR) for PrP(Sc) propagation in cultured cells and suggest that LRP/LR-specific antibodies could be used as powerful therapeutic tools in the treatment of transmissible spongiform encephalopathies.
Leucht
Christoph
C
Laboratorium für Molekulare Biologie-Genzentrum-Institut für Biochemie der LMU München, Feodor-Lynen Str. 25, D- 81377 Munich, Germany.
Simoneau
Steve
S
Rey
Clémence
C
Vana
Karen
K
Rieger
Roman
R
Lasmézas
Corinne Ida
CI
Weiss
Stefan
S
D000818:Animals; D001692:Biological Transport; D008970:Molecular Weight; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism*; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D016372:RNA, Antisense / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D017474:Receptors, Laminin / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases; D012608:Scrapie / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018620:PrPSc Proteins; D016372:RNA, Antisense; D034741:RNA, Small Interfering; D017474:Receptors, Laminin; D012260:Ribonucleases