Galectin-3 promotes lamellipodia formation in epithelial cells by interacting with complex N-glycans on α3β1 integrin

Chandrasseger Saravanan, Fu-Tong Liu, Ilene K. Gipson, Noorjahan Panjwani

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Recent studies have shown that galectin-3 (Gal-3; also known as LGALS3), a β-galactoside-binding lectin, promotes cell migration during re-epithelialization of corneal wounds. The goal of this study was to characterize the molecular mechanism by which Gal-3 stimulates cell migration. We demonstrate here that exogenous Gal-3, but not Gal-1 or Gal-8, promotes cell scattering and formation of lamellipodia in human corneal epithelial cells in a β-lactose-inhibitable manner. α3β1 integrin was identified as the major Gal-3-binding protein in corneal epithelial cells by affinity chromatography of cell lysates on a Gal-3-Sepharose column. Preincubation of cells with anti-α3 integrin function-blocking antibody significantly inhibited the induction of lamellipodia by Gal-3. Furthermore, exogenous Gal-3 activated both focal adhesion kinase, a key regulator of integrin-dependent intracellular signaling, and Rac1 GTPase, a member of the family of Rho GTPases, well known for its role in the reorganization of the actin cytoskeleton and formation of lamellipodial extensions. Experiments involving knockdown of β-1,6-N-acetylglucosaminytransferase V, an enzyme that synthesizes high-affinity glycan ligands for Gal-3, revealed that carbohydrate-mediated interaction between Gal-3 and complex N-glycans on α3β1 integrin plays a key role in Gal-3-induced lamellipodia formation. We propose that Gal-3 promotes epithelial cell migration by cross-linking MGAT5-modified complex N-glycans on α3β1 integrin and subsequently activating α3β1-integrin-Rac1 signaling to promote lamellipodia formation.

Original languageEnglish (US)
Pages (from-to)3684-3693
Number of pages10
JournalJournal of Cell Science
Volume122
Issue number20
DOIs
StatePublished - Oct 15 2009

Keywords

  • α3β1 integrin
  • Cell migration
  • Epithelium
  • Galectin-3
  • Lamellipodia

ASJC Scopus subject areas

  • Cell Biology

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