Different isoforms of the non-integrin laminin receptor are present in mouse brain and bind PrP.
The prion protein (PrP) plays a central role in prion diseases, and identifying its cellular receptor appears to be of crucial interest. We previously showed in the yeast two-hybrid system that PrP interacts with the 37 kDa precursor (LRP) of the high affinity 67 kDa laminin receptor (LR), which acts as the cellular receptor of PrP in cellular models. However, among the various isoforms of the receptor that have been identified so far, those which are present in the central nervous system and which bind PrP are still unknown. In this study, we have purified mouse brain fractions enriched in the laminin receptor and have performed overlay assays in order to identify those isoforms that interact with the prion protein. We demonstrate (i) the presence, in mouse brain, of several isoforms of the LRP/LR corresponding to different maturation states of the receptor (44, 60, 67 and 220 kDa) and (ii) the binding of all of these isoforms to PrP. Our data strongly support a physiological role of the laminin receptor/PrP interaction in the brain and highlight its relevance for transmissible spongiform encephalopathies.
Simoneau
Steve
S
CEA, Département de Recherche Médicale, DSV, B.P. 6, F-92 265 Fontenay-aux-Roses Cedex, France.
Haïk
Stéphane
S
Leucht
Christoph
C
Dormont
Dominique
D
Deslys
Jean-Philippe
JP
Weiss
Stefan
S
Lasmézas
Corinne
C
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D011328:Prions / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000302:isolation & purification / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D017474:Receptors, Laminin / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*
D000906:Antibodies; D016023:Integrins; D011328:Prions; D020033:Protein Isoforms; D017474:Receptors, Laminin