The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation Journal Articles uri icon

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abstract

  • Genes implicated in translation control have been associated with autism spectrum disorders (ASDs). However, some important genetic causes of autism, including the 16p11.2 microdeletion, bear no obvious connection to translation. Here, we use proteomics, genetics, and translation assays in cultured cells and mouse brain to reveal altered translation mediated by loss of the kinase TAOK2 in 16p11.2 deletion models. We show that TAOK2 associates with the translational machinery and functions as a translational brake by phosphorylating eukaryotic elongation factor 2 (eEF2). Previously, all signal-mediated regulation of translation elongation via eEF2 phosphorylation was believed to be mediated by a single kinase, eEF2K. However, we show that TAOK2 can directly phosphorylate eEF2 on the same regulatory site, but functions independently of eEF2K signaling. Collectively, our results reveal an eEF2K-independent signaling pathway for control of translation elongation and suggest altered translation as a molecular component in the etiology of some forms of ASD.

authors

  • Henis, Melad
  • Rücker, Tabitha
  • Scharrenberg, Robin
  • Richter, Melanie
  • Baltussen, Lucas
  • Hong, Shuai
  • Meka, Durga Praveen
  • Schwanke, Birgit
  • Neelagandan, Nagammal
  • Daaboul, Danie
  • Murtaza, Nadeem
  • Krisp, Christoph
  • Harder, Sönke
  • Schlüter, Hartmut
  • Kneussel, Matthias
  • Hermans-Borgmeyer, Irm
  • de Wit, Joris
  • Singh, Karun
  • Duncan, Kent E
  • de Anda, Froylan Calderón

publication date

  • April 12, 2024