TRIP-1 interacts with ezrin to regulate ezrin phosphorylation, cell protrusion formation and cell migration.

Cellular signalling

PubMedID: 24012495

Zhang H, Wan J, Huang L. TRIP-1 interacts with ezrin to regulate ezrin phosphorylation, cell protrusion formation and cell migration. Cell Signal. 2013;.
Cell migration is a molecular process crucial for embryonic morphogenesis, tissue repair, and disease progression in cancer. Cells migrate by extending protrusions, which are mediated by the assembly of a branched actin network. These protrusions can be either large and broad lamellipodia or spike-like filopodia. We found that TRIP-1, the TGF-ß receptor-interacting protein 1, played significant roles in TGF-ß-regulated cell protrusion by directly interacting with ezrin, a protein belongs to the ERM (ezrin-radixin-moesin) family. TRIP-1 interacted with ezrin both in vitro and in vivo. TRIP-1 interacted more intensely with activated ezrin. Immunofluorecence assay demonstrated TRIP-1 and ezrin colocalized at cell membrane, and the colocalization was affected by TGF-ß treatment. TRIP-1 knockdown increased ezrin phosphorylation and greatly promoted cell filopodial formation under serum or TGF-ß1 treatment. Migration assay showed that lack of TRIP-1 expression enhanced cell migration and overexpressed TRIP-1 inhibited cell migration induced by ezrin expression. We further showed that TRIP-1 expression inhibited filopodial formation, cell adhesion and migration induced by activated Cdc42. Our results indicate that TRIP-1 negatively regulates TGF-ß or Cdc42 induced filopodial formation by antagonizing with ezrin at leading edges of migrating cells. Our findings offer novel insights into the functional relationship between TRIP-1 and ezrin.