title: N-glycosylation of ß4 integrin controls the adhesion and motility of keratinocytes.
abstract: α6ß4 integrin is an essential component of hemidesmosomes and modulates cell migration in wound healing and cancer invasion. To elucidate the role of N-glycosylation on ß4 integrin, we investigated keratinocyte adhesion and migration through the re-expression of wild-type or N-glycosylation-defective ß4 integrin (ΔNß4) in ß4 integrin null keratinocytes. N-glycosylation of ß4 integrin was not essential for the heterodimer formation of ß4 integrin with α6 integrin and its expression on a cell surface, but N-glycosylation was required for integrin-mediated cell adhesion and migration. Concomitantly with the reduction of ß4 integrin in the membrane microdomain, the intracellular signals of Akt and ERK activation were decreased in cells expressing ΔNß4 integrin. Forced cross-linking of ß4 integrin rescued the decreased ERK activation in ΔNß4 integrin-expressing cells to a similar extent in wild-type ß4 integrin-expressing cells. Surprisingly, compared with cells expressing wild-type ß4 integrin, an alternation in N-glycan structures expressed on epidermal growth factor receptor (EGFR), and the induction of a stronger association between EGFR and ß4 integrin were observed in ΔNß4 integrin-expressing cells. These results clearly demonstrated that N-glycosylation on ß4 integrin plays an essential role in keratinocyte cellular function by allowing the appropriate complex formation on cell surfaces.
authors.affiliation: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai City, Miyagi, Japan. kariya@fmu.ac.jp
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kariya
authors.forename: Jianguo
authors.initials: J
authors.lastname: Gu
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D039663:Integrin beta4 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology*; D007797:Laminin / Q000378:metabolism; D008856:Microscopy, Fluorescence
chemical_list: D039663:Integrin beta4; D007797:Laminin
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