Abstract
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 language | English |
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Pages (from-to) | 1321-1329 |
Number of pages | 9 |
Journal | Journal of Cell Science |
Volume | 114 |
Issue number | Part 7 |
Publication status | Published - Apr 2001 |
Keywords
- 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