Deletion of Core Fucosylation on α3β1 Integrin Down-regulates Its Functions

Abstract

The core fucosylation (␣1,6-fucosylation) of glycoprotein is widely distributed in mammalian tissues. Recently ␣1,6-fucosylation has been further reported to be very crucial by the study of ␣1,6-fucosyltransferase (Fut8)-knock-out mice, which shows the phenotype of emphysema-like changes in the lung and severe growth retardation. In this study, we extensively investigated the effect of core fucosylation on ␣3␤1 integrin and found for the first time that Fut8 makes an important contribution to the functions of this integrin. The role of core fucosylation in ␣3␤1 integrin-mediated events has been studied by using Fut8 ؉/؉ and Fut8 ؊/؊ embryonic fibroblasts, respectively. We found that the core fucosylation of ␣3␤1 integrin, the major receptor for laminin 5, was abundant in Fut8 ؉/؉ cells but was totally abolished in Fut8 ؊/؊ cells, which was associated with the deficient migration mediated by ␣3␤1 integrin in Fut8 ؊/؊ cells. Moreover integrin-mediated cell signaling was reduced in Fut8؊/؊ cells. The reintroduction of Fut8 potentially restored laminin 5-induced migration and intracellular signaling. Collectively, these results suggested that core fucosylation is essential for the functions of ␣3␤1 integrin.␣1,6-Fucosyltransferase (Fut8) catalyzes the transfer of a fucose residue from GDP-fucose to position 6 of the innermost GlcNAc residue of the hybrid and complex types of N-linked oligosaccharides on the glycoproteins (Fig.

Glycan-related gene expression signatures in human metastatic hepatocellular carcinoma cells

“…Core fucosylation is of special interest due to its ability to modulate growth and development through altering functional properties of integrins. For example it has been shown that core decoration by α1,6 fucose of certain motifs of the α3β1 integrin complex is essential for its association and activity (11). Bisecting GlcNAc structure synthesized by MGAT3 was increased in HCCLM3 cells, data from the lectin microarray and GTs chip supported this finding.…”

“…The overexpressed bisecting GlcNAc structure on integrin down-regulated the binding capacity of integrin with its ligand, leading to reduced cell adhesion and cell migration (14). The introduction of the bisecting GlcNAc structure into the CD44 adhesion molecule promoted tumor formation and metastasis (11).…”

Alteration in N‐glycomics during mouse aging: a role for FUT8

“…In agreement, FUT8 activity measured in the livers of aging C57BL ⁄ 6 mice, dw ⁄ dw, and kl ⁄ kl mice was also correlated with the gene expression data and with age. FUT8 is known to play a key role in regulating physiological functions by modifying functional proteins to induce changes in TGF-b signaling, EGFR-mediated signaling, integrin a3b1-mediated cell adhesion, and VEGFR-2 expression (Wang et al, 2005(Wang et al, , 2006a(Wang et al, ,b, 2009Kondo et al, 2006;Zhao et al, 2006). Upregulation of FUT8 could have enormous effects on different signaling pathways and could thus influence the aging process.…”

GDP-mannose-4,6-dehydratase (GMDS) Deficiency Renders Colon Cancer Cells Resistant to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Receptor- and CD95-mediated Apoptosis by Inhibiting Complex II Formation

“…Fucosylation involves the attachment of an L-fucose residue to an oligosaccharide or protein and is one of the most important oligosaccharide modifications in cancer (13). Most cell surface receptors, including epidermal growth factor receptor (14), transforming growth factor-␤ receptor (15), E-cadherin (16), and integrins (17), are fucosylated. Fucosylated oligosaccharides regulate many physiological and pathological events, including cell growth, migration, embryogenesis, and tumor invasion, by affecting the folding and structure of these cell surface receptors (18).…”