NR AXGQ
AU Li,C.; Wong,P.; Pan,T.; Xiao,F.; Yin,S.; Chang,B.; Kang,S.C.; Ironside,J.; Sy,M.S.
TI Normal cellular prion protein is a ligand of selectins: binding requires Le(X) but is inhibited by sLe(X).
QU Biochemical Journal 2007 Sep 1; 406(2): 333-41
PT journal article; research support, n.i.h., extramural; research support, u.s. gov't, non-p.h.s.
AB The normal PrPc (cellular prion protein) contains sLe(X) [sialyl-Le(X) (Lewis X)] and Le(X). sLe(X) is a ligand of selectins. To examine whether PrPc is a ligand of selectins, we generated three human PrPc-Ig fusion proteins: one with Le(X), one with sLe(X), and the other with neither Le(X) nor sLe(X). Only Le(X)-PrPc-Ig binds E-, L- and P-selectins. Binding is Ca(2+)-dependent and occurs with nanomolar affinity. Removal of sialic acid on sLe(X)-PrPc-Ig enables the fusion protein to bind all selectins. These findings were confirmed with brain-derived PrPc. The selectins precipitated PrPc in human brain in a Ca(2+)-dependent manner. Treatment of brain homogenates with neuraminidase increased the amounts of PrPc precipitated. Therefore the presence of sialic acid prevents the binding of PrPc in human brain to selectins. Hence, human brain PrPc interacts with selectins in a manner that is distinct from interactions in peripheral tissues. Alternations in these interactions may have pathological consequences.
MH Animals; Antigens, CD15/immunology/*metabolism; Antigens, CD24/genetics/metabolism; Brain/drug effects/immunology/metabolism; Calcium/pharmacology; Cell Line; Epitopes/immunology; Gene Expression Regulation; Humans; Immunoglobulin G/genetics/immunology/metabolism; Lewis Blood-Group System; Ligands; Mice; Neuraminidase/metabolism; Oligosaccharides/immunology/*metabolism; Polysaccharides/metabolism; Prions/genetics/immunology/*metabolism; Protein Binding; Recombinant Fusion Proteins/genetics/metabolism; Selectins/*metabolism
AD Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44107-1712, U.S.A.
SP englisch
PO England