ABSTRACT
Cellular senescence is a highly stable cell-cycle arrest induced by DNA damage and various cellular stresses. Recently, we have revealed that lymphocyte antigen 6 complex, locus D (LY6D) is responsible for senescence-inducing stress-evoked vacuole formation through induction of Src family kinase (SFK)-mediated macropinocytosis. However, the signaling molecule(s) transducing the macropinocytosis signal from extracellular LY6D to the cytoplasmic SFK are unknown. In this study, we identified integrin ß1, a transmembrane signaling protein, as an interactor of LY6D by proteomic analysis and co-immunoprecipitation assays. Inhibition of integrin ß1 impaired LY6D-induced macropinocytosis, and integrin ß1 activated SFK through focal adhesion kinase to mediate macropinocytosis. These results indicate that integrin ß1 is a crucial mediator of the LY6D-induced vacuole formation in senescent cells.