FMRP recruitment of β‐catenin to the translation pre‐initiation complex represses translation. (25th October 2018) - Ehyai, Saviz
Abstract: Canonical Wnt/β‐catenin signaling is an essential regulator of various cellular functions throughout development and adulthood. Aberrant Wnt/β‐catenin signaling also contributes to various pathologies including cancer, necessitating an understanding of cell context‐dependent mechanisms regulating this pathway. Since protein–protein interactions underpin β‐catenin function and localization, we sought to identify novel β‐catenin interacting partners by affinity purification coupled with tandem mass spectrometry in vascular smooth muscle cells (VSMCs), where β‐catenin is involved in both physiological and pathological control of cell proliferation. Here, we report novel components of the VSMC β‐catenin interactome. Bioinformatic analysis of the protein networks implies potentially novel functions for β‐catenin, particularly in mRNA translation, and we confirm a direct interaction between β‐catenin and the fragile X mental retardation protein (FMRP). Biochemical studies reveal a basal recruitment of β‐catenin to the messenger ribonucleoprotein and translational pre‐initiation complex, fulfilling a translational repressor function. Wnt stimulation antagonizes this function, in part, by sequestering β‐catenin away from the pre‐initiation complex. In conclusion, we present evidence that β‐catenin fulfills a previously unrecognized function in translational repression. Synopsis: This study reports novel components of the β‐catenin interactome and identifies an β‐catenin/FMRP (fragile X mental retardation protein) complex with translational repressor function. Biochemical studies reveal recruitment of β‐catenin/FMRP to the translational pre‐initiation complex, fulfilling a translational repressor function. Wnt‐3a stimulation promotes β‐catenin re‐localization to the nucleus and concomitant de‐repression of translation. Abstract : This study reports novel components of the β‐catenin interactome and identifies an β‐catenin/FMRP (fragile X mental retardation protein) complex with translational repressor function.