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 β1, a transmembrane signaling protein, as an interactor of LY6D by proteomic analysis and co-immunoprecipitation assays. Inhibition of integrin β1 impaired LY6D-induced macropinocytosis, and integrin β1 activated SFK through focal adhesion kinase to mediate macropinocytosis. These results indicate that integrin β1 is a crucial mediator of the LY6D-induced vacuole formation in senescent cells.
Keywords: cellular senescence; endocytosis; membrane protein; signal transduction; vacuole.
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