Carboohydrate-carbohydrate binding of ganglioside to integrin alpha(5) modulates alpha(5)beta(1) function

Citation
Xq. Wang et al., Carboohydrate-carbohydrate binding of ganglioside to integrin alpha(5) modulates alpha(5)beta(1) function, J BIOL CHEM, 276(11), 2001, pp. 8436-8444
Citations number
44
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
276
Issue
11
Year of publication
2001
Pages
8436 - 8444
Database
ISI
SICI code
0021-9258(20010316)276:11<8436:CBOGTI>2.0.ZU;2-F
Abstract
Gangliosides GT1b and GD3, components of keratinocyte membranes, inhibit ke ratinocyte adhesion to fibronectin. Although ganglioside sialylation is kno wn to be important, the mechanism of inhibition is unknown. Using purified insect recombinant alpha (5) and beta (1) proteins and alpha (5)beta (1) in tegrin from lysed keratinocyte-derived SCC12 cells, we have shown that GT1b and GD3 inhibit the binding of alpha (5)beta (1) to fibronectin. Co-immuno precipitation of GT1b and alpha (5)beta (1) from SCC12 cells and direct bin ding of GT1b and GD3 to affinity-purified alpha (5)beta (1) from SCC12 cell s and insect recombinant alpha (5)beta (1), particularly the alpha (5) subu nit, further suggest interaction between ganglioside and alpha (5)beta (1). The carbohydrate moieties of integrin appear to be critical since ganglios ides are unable to bind deglycosylated forms of alpha (5)beta (1) from SCC1 2 and insect cells or poorly glycosylated recombinant alpha (5)beta (1) fro m Escherichia coli cells. The GT1b-alpha (5)beta (1) interaction is inhibit ed by concanavalin A, suggesting that GT1b binds to mannose structures in a lpha (5)beta (1). The preferential binding of GT1b to high mannose rather t han reduced mannose ovalbumin further implicates the binding of GT1b to man nose structures. These data provide evidence that highly sialylated ganglio sides regulate alpha (5)beta (1)-mediated adhesion of epithelial cells to f ibronectin through carbohydrate-carbohydrate interactions between GT1b and the alpha (5) subunit of alpha (5)beta (1) integrin.