Normal cellular prion protein is a ligand of selectins: binding requires Le(X) but is inhibited by sLe(X).
The normal PrP(C) (cellular prion protein) contains sLe(X) [sialyl-Le(X) (Lewis X)] and Le(X). sLe(X) is a ligand of selectins. To examine whether PrP(C) is a ligand of selectins, we generated three human PrP(C)-Ig fusion proteins: one with Le(X), one with sLe(X), and the other with neither Le(X) nor sLe(X). Only Le(X)-PrP(C)-Ig binds E-, L- and P-selectins. Binding is Ca(2+)-dependent and occurs with nanomolar affinity. Removal of sialic acid on sLe(X)-PrP(C)-Ig enables the fusion protein to bind all selectins. These findings were confirmed with brain-derived PrP(C). The selectins precipitated PrP(C) in human brain in a Ca(2+)-dependent manner. Treatment of brain homogenates with neuraminidase increased the amounts of PrP(C) precipitated. Therefore the presence of sialic acid prevents the binding of PrP(C) in human brain to selectins. Hence, human brain PrP(C) interacts with selectins in a manner that is distinct from interactions in peripheral tissues. Alternations in these interactions may have pathological consequences.
Li
Chaoyang
C
Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44107-1712, U.S.A.
Wong
Poki
P
Pan
Tao
T
Xiao
Fan
F
Yin
Shaoman
S
Chang
Binggong
B
Kang
Shin-Chung
SC
Ironside
James
J
Sy
Man-Sun
MS
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D009439:Neuraminidase / Q000378:metabolism; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019087:Selectins / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen
D051927:CD24 Antigen; D000939:Epitopes; D007074:Immunoglobulin G; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D008024:Ligands; D009844:Oligosaccharides; D011134:Polysaccharides; D011328:Prions; D011993:Recombinant Fusion Proteins; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D009439:Neuraminidase; D002118:Calcium