Normal cellular prion protein is a ligand of selectins: binding requires Le(X) but is inhibited by sLe(X)

Chaoyang Li, Poki Wong, Tao Pan, Fan Xiao, Shaoman Yin, Binggong Chang, Shin-Chung Kang, James Ironside, Man-Sun Sy

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)333-41
Number of pages9
JournalBiochemical Journal
Volume406
Issue number2
DOIs
Publication statusPublished - 1 Sep 2007

Keywords

  • Animals
  • Antigens, CD15
  • Antigens, CD24
  • Brain
  • Calcium
  • Cell Line
  • Epitopes
  • Gene Expression Regulation
  • Humans
  • Immunoglobulin G
  • Lewis Blood-Group System
  • Ligands
  • Mice
  • Neuraminidase
  • Oligosaccharides
  • Polysaccharides
  • Prions
  • Protein Binding
  • Recombinant Fusion Proteins
  • Selectins

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