title: Importance of membrane-proximal N-glycosylation on integrin β1 in its activation and complex formation.
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.
authors: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Miyagi, Japan.
authors: Sicong
authors: S
authors: Hou
authors: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Miyagi, Japan.
authors: Qinglei
authors: Q
authors: Hang
authors: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Miyagi, Japan.
authors: Tomoya
authors: T
authors: Isaji
authors: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Miyagi, Japan.
authors: Jishun
authors: J
authors: Lu
authors: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Miyagi, Japan.
authors: Tomohiko
authors: T
authors: Fukuda
authors: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Miyagi, Japan jgu@tohoku-mpu.ac.jp.
authors: Jianguo
authors: J
authors: Gu
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D003412:Cricetulus; D066246:ErbB Receptors / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D053671:Syndecan-4 / Q000378:metabolism
chemical_list: D039081:Integrin alpha5beta1; D019012:Integrin beta1; C508304:SDC4 protein, human; D053671:Syndecan-4; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: cell migration; cell signaling; sialylation