The 37 kDa/67 kDa laminin receptor is required for PrP^Sc propagation in scrapie‐infected neuronal cells

Abstract

The accumulation of PrPSc 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 PrPSc in these cells. The treatments also reduced PrPc levels. The anti‐LRP/LR antibody, W3, abolished PrPSc accumulation and reduced PrPc levels after seven days of incubation. Cells remained free of PrPSc after being cultured for 14 additional days without the antibody, whereas the PrPc level was restored. Our results demonstrate the necessity of the laminin receptor (LRP/LR) for PrPSc 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.

Pathological Prion Protein Exposure Switches on Neuronal Mitogen-activated Protein Kinase Pathway Resulting in Microglia Recruitment

“…As well, the laminin receptor has been shown to bind and internalize PrPc (30) and is thought to be also involved in PrPres binding. Specific antibodies developed against the laminin receptor inhibit the accumulation of the pathological isoform, PrPres in N2a neuroblastoma cells (37). In our model, neither PrPc nor the laminin receptor are involved in the neuronal cell response induced by PrPres.…”

Intra- and Interspecies Interactions between Prion Proteins and Effects of Mutations and Polymorphisms

“…Here the sugars seem to have an effect on the residual nickel binding since the non-glycosylated band does not interact with the nickel column. As positive controls the PrP interacting proteins 37 kDa laminin receptor precursor (LRP; Rieger et al, 1997;Gauczynski et al, 2001b;Hundt et al, 2001;Leucht et al, 2003;Simoneau et al, 2003) and Hsp60 (Edenhofer et al, 1996) (lane 1), both tagged with FLAG, were used. Both proteins bound to oligohistidine-tagged PrP (lane 1 and 2, respectively).…”

Heparan Sulfate and Heparin Promote Faithful Prion Replication in Vitro by Binding to Normal and Abnormal Prion Proteins in Protein Misfolding Cyclic Amplification

“…Prions consist primarily of a pathogenic form (PrP Sc ) of the normal cellular prion protein (PrP C ), and PrP Sc appears to propagate itself through the autocatalytic conformational conversion of PrP C (2). Although the mechanism of PrP C conversion into PrP Sc remains unclear, host cofactors have been suggested to be necessary for efficient replication of PrP Sc (3,4); various biological molecules, such as nucleic acids (5)(6)(7)(8), glycosaminoglycans (GAGs) (9 -12), lipids (13,14), and proteins (15)(16)(17), have been reported to act as cofactors for PrP C conversion into PrP Sc .…”