Necl-5/Poliovirus Receptor Interacts in cis with Integrin αVβ3 and Regulates Its Clustering and Focal Complex Formation

Abstract Integrin αvβ3, which forms focal complexes at leading edges in moving cells, is up-regulated in cancer cells and so is implicated in their invasiveness. Necl-5, originally identified as a poliovirus receptor and also up-regulated in cancer cells, colocalizes with integrin αvβ3 at leading edges in moving cells and enhances growth factor-induced cell movement. Here, we show that Necl-5 interacts directly, in cis, with integrin αvβ3, and enhances integrin αvβ3 clustering and focal complex formation at leading edges in NIH3T3 cells. The extracellular region of Necl-5, but not the cytoplasmic region, is necessary for its interaction with integrin αvβ3; however, both regions are necessary for its action. An interaction between integrin αvβ3 and vitronectin and PDGF-induced activation of Rac are also necessary for integrin αvβ3 clustering. The interaction between Necl-5 and integrin αvβ3 enhances PDGF-induced Rac activation, facilitating integrin αvβ3 clustering presumably in a feedback amplification manner. Thus, Necl-5 has a critical role in integrin αvβ3 clustering and focal complex formation.