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

Tropoelastin protein monomers assemble to form elastin. Cellular integrin α_Vβ₃ 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 α_V integrin(s) and integrin α_Vβ₅ specifically were critical for cell adhesion to this part of tropoelastin. These data reveal a common α_V integrin-binding theme for tropoelastin: α_Vβ₃ at the C terminus and α_Vβ₅ at the central region of tropoelastin. Each α_V region contributes to fibroblast attachment and spreading, but they differ in their effects on cytoskeletal assembly.