Differential galactosylation of neuronal and haematopoietic signal regulatory protein-alpha determines its cellular binding-specificity

I. M. van den Nieuwenhof, C. Renardel de Lavalette, N. Diaz, I. van Die, T. K. van den Berg

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22 Citations (Scopus)


Signal regulatory protein-alpha (SIRP alpha) is a member of the Ig superfamily selectively expressed by neuronal and myeloid cells. The molecule mediates functional interactions with CD47/integrin-associated protein. Here we provide evidence for the tissue-specific glycosylation of neuronal and haematopoietic SIRP alpha. We demonstrate a major difference in the galactosylation of N-linked glycans isolated from neuronal (i.e. brain-derived) SIRP alpha as compared to myeloid (i.e. spleen-derived) SIRP alpha, with neuronal SIRP alpha almost completely lacking galactose. beta 4-galactosyltransferase assays demonstrated that this is most likely due to a low galactosylation capacity of the brain. In order to investigate the role of galactosylation of SIRP alpha in cellular interactions, soluble recombinant SIRP alpha glycoforms containing galactose (SIRP alpha-Fc) or lacking galactose (SIRP alpha(Delta Gal)-Fc) were produced. Binding studies demonstrated superior binding of SIRP alpha(Delta Gal)-Fc to cerebellar neurons and isolated lymphocytes. In contrast, SIRP alpha-Fc bound relatively strong to macrophages. These data show that the galactosylation of SIRP alpha determines its cellular binding specificity
Original languageEnglish
Pages (from-to)1321-1329
Number of pages9
JournalJournal of Cell Science
Issue numberPart 7
Publication statusPublished - Apr 2001


  • Animals
  • Antigens, Differentiation
  • CHO Cells
  • Cricetinae
  • Galactose/metabolism
  • Glycosylation
  • Humans
  • Immunoglobulin Fc Fragments/biosynthesis
  • Membrane Glycoproteins/biosynthesis
  • N-Acetyllactosamine Synthase/metabolism
  • Neural Cell Adhesion Molecule L1
  • Neural Cell Adhesion Molecules/biosynthesis
  • Neurons/metabolism
  • PC12 Cells
  • Polysaccharides/metabolism
  • Rats
  • Receptors, Immunologic
  • Recombinant Fusion Proteins/biosynthesis

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