Galectin-3 promotes lamellipodia formation in epithelial cells by interacting with complex N-glycans on α3β1 integrin
Galectin-3 promotes lamellipodia formation in epithelial cells by interacting with complex N-glycans on α3β1 integrin
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DOI：
10.1242/jcs.045674
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发表时间：
2009-10-15
影响因子：
4
通讯作者：
Panjwani, Noorjahan
中科院分区：
文献类型：
--
作者：
Saravanan, Chandrassegar;Liu, Fu-Tong;Panjwani, Noorjahan
最近的研究表明，半乳糖凝集素-3（Gal-3；也称为 LGALS3）是一种 β-半乳糖苷结合凝集素，可促进角膜伤口上皮再生过程中的细胞迁移。本研究的目的是表征 Gal-3 刺激细胞迁移的分子机制。我们在此证明，外源性 Gal-3（而非 Gal-1 或 Gal-8）以 β-乳糖抑制方式促进人角膜上皮细胞中的细胞分散和板状伪足的形成。通过在 Gal-3-Sepharose 柱上对细胞裂解物进行亲和层析，将 α3β1 整联蛋白鉴定为角膜上皮细胞中主要的 Gal-3 结合蛋白。将细胞与抗α3整合素功能阻断抗体预孵育可显着抑制Gal-3对板状伪足的诱导。此外，外源性 Gal-3 激活粘着斑激酶（整合素依赖性细胞内信号转导的关键调节因子）和 Rac1 GTPase（Rho GTPases 家族成员），以其在肌动蛋白细胞骨架重组和板状足延伸形成中的作用而闻名。涉及敲低 beta-1,6-N-乙酰葡糖胺转移酶 V（一种为 Gal-3 合成高亲和力聚糖配体的酶）的实验表明，Gal-3 与 α 3 beta 1 整联蛋白上的复合 N-聚糖之间碳水化合物介导的相互作用在 Gal-3 诱导的板状伪足形成中发挥着关键作用。我们提出 Gal-3 通过在 α 3 β 1 整合素上交联 MGAT5 修饰的复合 N-聚糖并随后激活 α 3 β 1 整合素-Rac1 信号传导以促进板状伪足的形成来促进上皮细胞迁移。
Recent studies have shown that galectin-3 (Gal-3; also known as LGALS3), a beta-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 beta-lactose-inhibitable manner alpha 3 beta 1 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-alpha 3 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 beta-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 alpha 3 beta 1 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 alpha 3 beta 1 integrin and subsequently activating alpha 3 beta 1-integrin-Rac1 signaling to promote lamellipodia formation.