Importance of membrane‐proximal N‐glycosylation on integrin α1 in its activation and complex formation. Issue 12 (26th August 2016)

• Record Type: Journal Article
• Authors: Hou, Sicong; Hang, Qinglei; Isaji, Tomoya; Lu, Jishun; Fukuda, Tomohiko; Gu1, Jianguo
• Is Part Of: FASEB journal. Volume 30:Issue 12(2016)
• Page Start: 4120
• Page End: 4131
• Publication Date: 2016-08-26
• Subjects: cell migration -- cell signaling -- sialylation; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201600665R
• Languages: English
• ISSNs: 0892-6638

Abstract

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 themembrane‐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 where in N ‐glycosy lationnear 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 ofmembrane‐proximal N ‐glycosylation on integrin β1 in its activation and complex formation. FASEB J. 30, 4120–4131 (2016). www.fasebj.org