| Research Abstract |
Glycosylation is involved in a variety of physiological and pathological events, including cell growth, migration, differentiation and tumor invasion. Branched N-glycans, such as bisecting GlcNAc, β1, 6 GlcNAc and core fucose (α1, 6 fucose), are enzymatic products of GnT-III, GnT-V and Fut8, respectively. These branched structures are highly associated with various biological functions of cell adhesion molecules, including cell adhesion and cancer metastasis. We have found Following: 1), α3β1 integrin could be modified by either GnT-III or GnT-V, and GnT-III inhibited GnT-V-stimulated α3β1 integrin-mediated cell migration. The priority of GnT-III for modification of the α3 subunit may explain inhibition of GnT V-induced cell migration by GnT-III. These results were the first to demonstrate that GnT-III and GnT-V competitively modify the same target glycoprotein and that this competition between enzymes either positively or negatively regulates the biological function of the target protein. 2), the role of core fucosylation in α3β1 integrin-mediated events has been studied using Fut8^<+/+> and Fut8^<-/-> embryonic fibroblasts. α3β1 integrin-mediated migration was reduced in Fut8^<-/-> cells. Reintroduction of Fut8 has the potential to reverse such impairments, suggesting that core fucosylation is essential for functional α3β1 integrin. 3), integrins have multiple potential N-glycosylation sites, only N-glycans located on certain motifs regulate integrin conformation and biological function. For example, only N-glycans located on either the β-propeller of α5 integrin contribute to the regulation of integrin function.
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