Departamento de Biología Celular e Inmunología, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
Departamento de Biología Molecular, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain.
Front Immunol. 2018 Nov 5;9:2474. doi: 10.3389/fimmu.2018.02474. eCollection 2018.
Integrin α5β1 is a crucial adhesion molecule that mediates the adherence of many cell types to the extracellular matrix through recognition of its classic ligand fibronectin as well as to other cells through binding to an alternative counter-receptor, the metalloproteinase ADAM17/TACE. Interactions between integrin α5β1 and ADAM17 may take place both in (between molecules expressed on different cells) or in (between molecules expressed on the same cell) configurations. It has been recently reported that the association between α5β1 and ADAM17 keeps both molecules inactive, whereas their dissociation results in activation of their adhesive and metalloproteinase activities. Here we show that the tetraspanin CD9 negatively regulates integrin α5β1-mediated cell adhesion by enhancing the interaction of this integrin with ADAM17 on the cell surface. Additionally we show that, similarly to CD9, the monoclonal antibody 2A10 directed to the disintegrin domain of ADAM17 specifically inhibits integrin α5β1-mediated cell adhesion to its ligands fibronectin and ADAM17.
整合素 α5β1 是一种至关重要的黏附分子，通过识别其经典配体纤连蛋白以及通过与另一种替代的受体金属蛋白酶 ADAM17/TACE 结合来介导许多细胞类型与细胞外基质以及其他细胞的黏附。整合素 α5β1 和 ADAM17 之间的相互作用可以发生在 （在不同细胞表达的分子之间）或 （在同一细胞表达的分子之间）的构型中。最近有报道称，α5β1 和 ADAM17 之间的 关联使这两种分子保持非活性状态，而它们的解离导致其黏附活性和金属蛋白酶活性的激活。在这里，我们表明四跨膜蛋白 CD9 通过增强整合素 α5β1 与细胞表面上的 ADAM17 的 相互作用来负调控整合素 α5β1 介导的细胞黏附。此外，我们表明，类似于 CD9，针对 ADAM17 的解整合素结构域的单克隆抗体 2A10 特异性抑制整合素 α5β1 与其配体纤连蛋白和 ADAM17 的细胞黏附。
