A Novel Cell Adhesion Region in Tropoelastin Mediates Attachment to Integrin αVβ5

Background: Cellular integrin (V3) binds to RKRK at the C-terminal tail of tropoelastin. Results: Inhibition of integrin (V5) hinders cell adhesion to tropoelastin constructs comprising domains 17 and 18. Conclusion: Integrin (V5) mediates cell adhesion to tropoelastin through a central region. Significance: Understanding the cell adhesion activity of tropoelastin gives improved insight into the physiological and pathological cell responses to this protein. Tropoelastin protein monomers assemble to form elastin. Cellular integrin (V3) binds RKRK at the C-terminal tail of tropoelastin. We probed cell interactions with tropoelastin by deleting the RKRK sequence to identify other cell-binding interactions within tropoelastin. We found a novel human dermal fibroblast attachment and spreading site on tropoelastin that is located centrally in the molecule. Inhibition studies demonstrated that this cell adhesion was not mediated by either elastin-binding protein or glycosaminoglycans. Cell interactions were divalent cation-dependent, indicating integrin dependence. Function-blocking monoclonal antibodies revealed that (V) integrin(s) and integrin (V5) specifically were critical for cell adhesion to this part of tropoelastin. These data reveal a common (V) integrin-binding theme for tropoelastin: (V3) at the C terminus and (V5) at the central region of tropoelastin. Each (V) region contributes to fibroblast attachment and spreading, but they differ in their effects on cytoskeletal assembly.