RRC ID 52090
著者 Hang Q, Isaji T, Hou S, Wang Y, Fukuda T, Gu J.
タイトル A Key Regulator of Cell Adhesion: Identification and Characterization of Important N-Glycosylation Sites on Integrin α5 for Cell Migration.
ジャーナル Mol Cell Biol
Abstract The N-glycosylation of integrin α5β1 is thought to control many fundamental aspects of cell behavior, including cell adhesion and migration. However, the mechanism of how N-glycans function remains largely obscure. Here, we used a loss-of-function approach. Wild-type (WT) integrin α5 and N-glycosylation mutant S3-5 (sites 3 to 5) integrin α5, which contains fewer N-glycans, were stably reconstituted in α5 knockout cancer cells. We found that the migration ability of S3-5 cells was decreased in comparison with that of the WT. Interestingly, the levels of phosphorylated focal adhesion kinase and actin stress fiber formation were greatly enhanced in the S3-5 mutant. In a mechanistic manner, the internalization of active but not total integrin α5β1 was inhibited in S3-5 cells, which is a process that is related to the enhanced expression of active integrin α5β1 on the cell surface. Importantly, restoration of N-glycosylation on the β-propeller domain of α5 reinstated the cell migration ability, active α5β1 expression, and internalization. Moreover, these N-glycans are critical for α5-syndecan-4 complex formation. These findings indicate that N-glycosylation on the β-propeller domain functions as a molecular switch to control the dynamics of α5β1 on the cell surface that in turn is required for optimum adhesion for cell migration.
巻・号 37(9)
公開日 2017-5-1
DOI 10.1128/MCB.00558-16
PII MCB.00558-16
PMID 28167607
PMC PMC5394273
MeSH Cell Adhesion / physiology* Cell Line, Tumor Cell Membrane / metabolism* Cell Movement / physiology* Focal Adhesion Kinase 1 / metabolism Glycosylation HEK293 Cells HeLa Cells Humans Integrin alpha5beta1 / metabolism* Multiprotein Complexes / metabolism Phosphorylation Protein Structure, Tertiary Syndecan-4 / metabolism
IF 3.611
引用数 17
リソース情報
ヒト・動物細胞 293T(RCB2202) HeLa