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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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)1321-9
Number of pages9
JournalJournal of Cell Science
Issue numberPt 7
Publication statusPublished - Apr 2001

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