| Abstract |
N-Glycosylation of integrin α5β1 plays important roles in cell biologic functions; however, the mechanisms that underlie those roles remain poorly understood. Here, we present evidence that the membrane-proximal N-glycosylation on integrin β1 could positively regulate cell migration by promoting β1 activation. The S4-6 β1 mutant contains only 3 N-glycosylation sites, which are essential for α5 and β1 heterodimer formation, and despite only a small difference in expression levels of α5β1 between wild-type and S4-6 mutant, cell spreading and migration of the S4-6 mutant was significantly decreased compared with that of control. Consistent with these phenotypes, β1-mediated cellular signaling and its activation were clearly suppressed in the S4-6 mutant. Of note, these developments could be rescued by restoration of N-glycosylation sites in the membrane-proximal domain. Further study on the regulatory mechanisms suggested that membrane-proximal N-glycosylation is critical for intermolecular interactions between integrin β1 and other cell membrane proteins, such as syndecan-4 and epidermal growth factor receptor. Moreover, α2,6-sialylation is required for β1 activation. These data suggest a novel regulatory mechanism wherein N-glycosylation near the cell membrane on β1 may serve as a platform that facilitates its complex formation on the cell membrane, thereby affecting integrin-mediated functions.-Hou, S., Hang, Q., Isaji, T., Lu, J., Fukuda, T., Gu, J. Importance of membrane-proximal N-glycosylation on integrin β1 in its activation and complex formation.
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