Carbohydrate-Carbohydrate Binding of Ganglioside to Integrin α 5 Modulates α5β1 Function

Xiaoqi Wang, Ping Sun, Abbas Al-Qamari, Tadashi Tai, Ikuo Kawashima, Amy S. Paller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Gangliosides GT1b and GD3, components of keratinocyte membranes, inhibit keratinocyte adhesion to fibronectin. Although ganglioside sialylation is known to be important, the mechanism of inhibition is unknown. Using purified insect recombinant α5 and β1 proteins and α 5β1 integrin from lysed keratinocyte-derived SCC12 cells, we have shown that GT1b and GD3 inhibit the binding of α 5β1 to fibronectin. Co-immunoprecipitation of GT1b and α5β1 from SCC12 cells and direct binding of GT1b and GD3 to affinity-purified α5β15 from SCC12 cells and insect recombinant α5β1, particularly the α5 subunit, further suggest interaction between ganglioside and α5β1. The carbohydrate moieties of integrin appear to be critical since gangliosides are unable to bind deglycosylated forms of α5β1 from SCC12 and insect cells or poorly glycosylated recombinant α5β 1 from Escherichia coli cells. The GT1b-α5β 1 interaction is inhibited by concanavalin A, suggesting that GT1b binds to mannose structures in α5β1. The preferential binding of GT1b to high mannose rather than reduced mannose ovalbumin further implicates the binding of GT1b to mannose structures. These data provide evidence that highly sialylated gangliosides regulate α 5β1-mediated adhesion of epithelial cells to fibronectin through carbohydrate-carbohydrate interactions between GT1b and the α5 subunit of α5β1 integrin.

Original languageEnglish (US)
Pages (from-to)8436-8444
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number11
DOIs
StatePublished - Mar 16 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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