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The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation.
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 K; Duncan, Kent E; de Anda, Froylan Calderón.
Afiliación
  • Henis M; Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • Rücker T; Department of Anatomy and Embryology, Faculty of Veterinary Medicine, New Valley University, 72511 El-Kharga, Egypt.
  • Scharrenberg R; Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • Richter M; Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • Baltussen L; Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • Hong S; VIB Center for Brain & Disease Research, Herestraat 49, 3000 Leuven, Belgium.
  • Meka DP; KU Leuven Department of Neurosciences, Leuven Brain Institute, Herestraat 49, 3000 Leuven, Belgium.
  • Schwanke B; Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • Neelagandan N; Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • Daaboul D; Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • Murtaza N; Neuronal Translational Control Group, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Falkenried 94, 20251 Hamburg, Germany.
  • Krisp C; Institute of Bioengineering (IBI), École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
  • Harder S; VIB Center for Brain & Disease Research, Herestraat 49, 3000 Leuven, Belgium.
  • Schlüter H; KU Leuven Department of Neurosciences, Leuven Brain Institute, Herestraat 49, 3000 Leuven, Belgium.
  • Kneussel M; Krembil Research Institute, Donald K. Johnson Eye Institute, University Health Network, 60 Leonard Ave, Toronto, Ontario M5T 0S8, Canada.
  • Hermans-Borgmeyer I; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario L8S 4A9, Canada.
  • de Wit J; Institute for Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics Group, Campus Forschung, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany.
  • Singh KK; Institute for Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics Group, Campus Forschung, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany.
  • Duncan KE; Institute for Clinical Chemistry and Laboratory Medicine, Mass Spectrometric Proteomics Group, Campus Forschung, University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany.
  • de Anda FC; Institute of Neurogenetics, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, Germany.
Sci Adv ; 10(15): eadf7001, 2024 Apr 12.
Article en En | MEDLINE | ID: mdl-38608030
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Autístico / Ursidae / Trastorno del Espectro Autista Límite: Animals Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Autístico / Ursidae / Trastorno del Espectro Autista Límite: Animals Idioma: En Revista: Sci Adv Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos