The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation

Mauricio M. Oliveira, Muhaned Mohamed, Megan K. Elder, Keylin Banegas-Morales, Maggie Mamcarz, Emily H. Lu, Ela A.N. Golhan, Nishika Navrange, Snehajyoti Chatterjee, Ted Abel, Eric Klann

Research output: Contribution to journalArticlepeer-review


Neuronal protein synthesis is required for long-lasting plasticity and long-term memory consolidation. Dephosphorylation of eukaryotic initiation factor 2α is one of the key translational control events that is required to increase de novo protein synthesis that underlies long-lasting plasticity and memory consolidation. Here, we interrogate the molecular pathways of translational control that are triggered by neuronal stimulation with brain-derived neurotrophic factor (BDNF), which results in eukaryotic initiation factor 2α (eIF2α) dephosphorylation and increases in de novo protein synthesis. Primary rodent neurons exposed to BDNF display elevated translation of GADD34, which facilitates eIF2α dephosphorylation and subsequent de novo protein synthesis. Furthermore, GADD34 requires G-actin generated by cofilin to dephosphorylate eIF2α and enhance protein synthesis. Finally, GADD34 is required for BDNF-induced translation of synaptic plasticity-related proteins. Overall, we provide evidence that neurons repurpose GADD34, an effector of the integrated stress response, as an orchestrator of rapid increases in eIF2-dependent translation in response to plasticity-inducing stimuli.

Original languageEnglish (US)
Article number113670
JournalCell Reports
Issue number2
StatePublished - Feb 27 2024


  • BDNF
  • CP: Molecular biology
  • CP: Neuroscience
  • GADD34
  • cytoskeleton
  • eIF2α
  • local translation
  • mRNA translation
  • neuron
  • neuronal plasticity
  • protein synthesis
  • synaptic plasticity

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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