The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein.
Recently, we identified the 37-kDa laminin receptor precursor (LRP) as an interactor for the prion protein (PrP). Here, we show the presence of the 37-kDa LRP and its mature 67-kDa form termed high-affinity laminin receptor (LR) in plasma membrane fractions of N2a cells, whereas only the 37-kDa LRP was detected in baby hamster kidney (BHK) cells. PrP co-localizes with LRP/LR on the surface of N2a cells and Semliki Forest virus (SFV) RNA transfected BHK cells. Cell-binding assays reveal the LRP/LR-dependent binding of cellular PrP by neuronal and non-neuronal cells. Hyperexpression of LRP on the surface of BHK cells results in the binding of exogenous PrP. Cell binding is similar in PrP(+/+) and PrP(0/0) primary neurons, demonstrating that PrP does not act as a co-receptor of LRP/LR. LRP/LR-dependent internalization of PrP is blocked at 4 degrees C. Secretion of an LRP mutant lacking the transmembrane domain (aa 86-101) from BHK cells abolishes PrP binding and internalization. Our results show that LRP/LR acts as the receptor for cellular PrP on the surface of mammalian cells.
Gauczynski
S
S
Laboratorium für Molekulare Biologie-Genzentrum-Institut für Biochemie der LMU München, Feodor-Lynen Str. 25, D-81377 Munich, Germany.
Peyrin
J M
JM
Haïk
S
S
Leucht
C
C
Hundt
C
C
Rieger
R
R
Krasemann
S
S
Deslys
J P
JP
Dormont
D
D
Lasmézas
C I
CI
Weiss
S
S
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D005434:Flow Cytometry; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D017096:Prion Diseases / Q000209:etiology; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012672:Semliki forest virus / Q000235:genetics; D014162:Transfection
D009842:Oligopeptides; D010455:Peptides; D011328:Prions; D011498:Protein Precursors; D017474:Receptors, Laminin; D011993:Recombinant Fusion Proteins; C085706:FLAG peptide