The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells.
Prions are thought to consist of infectious proteins that cause transmissible spongiform encephalopathies. According to overwhelming evidence, the pathogenic prion protein PrPSc converts its host encoded isoform PrPC into insoluble aggregates of PrPSc, concomitant with pathological modifications (for review, see refs. 1-3). Although the physiological role of PrPC is poorly understood, studies with PrP knockout mice demonstrated that PrPC is required for the development of prion diseases. Using the yeast two-hybrid technology in Saccharomyces cerevisiae, we identified the 37-kDa laminin receptor precursor (LRP) as interacting with the cellular prion protein PrPC. Mapping analysis of the LRP-PrP interaction site in S. cerevisiae revealed that PrP and laminin share the same binding domain (amino acids 161 to 180) on LRP. The LRP-PrP interaction was confirmed in vivo in insect (Sf9) and mammalian cells (COS-7). The LRP level was increased in scrapie-infected murine N2a cells and in brain and spleen of scrapie-infected mice. In contrast, the LRP concentration was not significantly altered in these organs from mice infected with the bovine spongiform encephalopathic agent (BSE), which have a lower PrPSc accumulation. LRP levels, however, were dramatically increased in brain and pancreas, slightly increased in the spleen and not altered in the liver of crapie-infected hamsters. These data show that enhanced LRP concentrations are correlated with PrPSc accumulation in organs from mice and hamsters. The laminin receptor precursor, which is highly conserved among mammals and is located on the cell surface, may act as a receptor or co-receptor for the prion protein on mammalian cells.
Rieger
R
R
Laboratorium für Molekulare Biologie-Genzentrum-Institut für Biochemie der LMU München, Munich, Germany.
Edenhofer
F
F
Lasmézas
C I
CI
Weiss
S
S
D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D006224:Cricetinae; D005057:Eukaryotic Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018620:PrPSc Proteins / Q000378:metabolism*; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D017474:Receptors, Laminin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology
D000199:Actins; D018620:PrPSc Proteins; D011498:Protein Precursors; D017474:Receptors, Laminin; D011993:Recombinant Fusion Proteins