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Article

FMRP recruitment of β‐catenin to the translation pre‐initiation complex represses translation

Saviz Ehyai, Tetsuaki Miyake, Declan Williams, Jyotsna Vinayak, Mark A Bayfield, View ORCID ProfileJohn C McDermott
DOI 10.15252/embr.201745536 | Published online 25.10.2018
EMBO reports (2018) e45536
Saviz Ehyai
Department of Biology, York University, Toronto, ON, CanadaMuscle Health Research Centre (MHRC), York University, Toronto, ON, CanadaCentre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, Canada
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Tetsuaki Miyake
Department of Biology, York University, Toronto, ON, CanadaMuscle Health Research Centre (MHRC), York University, Toronto, ON, CanadaCentre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, Canada
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Declan Williams
Department of Chemistry, York University, Toronto, ON, CanadaCentre for Research in Mass Spectrometry (CRMS), York University, Toronto, ON, Canada
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Jyotsna Vinayak
Department of Biology, York University, Toronto, ON, CanadaCentre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, Canada
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Mark A Bayfield
Department of Biology, York University, Toronto, ON, CanadaCentre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, Canada
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John C McDermott
Department of Biology, York University, Toronto, ON, CanadaMuscle Health Research Centre (MHRC), York University, Toronto, ON, CanadaCentre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, CanadaDepartment of Chemistry, York University, Toronto, ON, CanadaCentre for Research in Mass Spectrometry (CRMS), York University, Toronto, ON, Canada
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Author Affiliations

  1. Saviz Ehyai1,2,3,6,
  2. Tetsuaki Miyake1,2,3,
  3. Declan Williams4,5,7,
  4. Jyotsna Vinayak1,3,
  5. Mark A Bayfield1,3 and
  6. John C McDermott (jmcderm{at}yorku.ca)*,1,2,3,4,5
  1. 1Department of Biology, York University, Toronto, ON, Canada
  2. 2Muscle Health Research Centre (MHRC), York University, Toronto, ON, Canada
  3. 3Centre for Research in Biomolecular Interactions (CRBI), York University, Toronto, ON, Canada
  4. 4Department of Chemistry, York University, Toronto, ON, Canada
  5. 5Centre for Research in Mass Spectrometry (CRMS), York University, Toronto, ON, Canada
  6. 6Present Address: Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
  7. 7Present Address: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  1. ↵*Corresponding author. Tel: +1 416 736 2100x30344; Fax: +1 416 736 5698; E‐mail: jmcderm{at}yorku.ca
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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

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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.

  • β‐catenin
  • FMRP
  • mRNA translation
  • pre‐initiation complex
  • Wnt signaling

EMBO Reports (2018) e45536

  • Received November 23, 2017.
  • Revision received September 12, 2018.
  • Accepted September 19, 2018.
  • © 2018 The Authors
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Volume 20, Issue 2
01 February 2019
EMBO reports: 20 (2)
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