The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation
Summary: 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 plast...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-02-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723016819 |
| _version_ | 1797291801265045504 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Mauricio M. Oliveira |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-07T19:42:59Z |
| format | Article |
| id | doaj.art-ec977505ce0440bead73395783f6d0fd |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T19:42:59Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ec977505ce0440bead73395783f6d0fd2024-02-29T05:18:32ZengElsevierCell Reports2211-12472024-02-01432113670The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translationMauricio M. Oliveira0Muhaned Mohamed1Megan K. Elder2Keylin Banegas-Morales3Maggie Mamcarz4Emily H. Lu5Ela A.N. Golhan6Nishika Navrange7Snehajyoti Chatterjee8Ted Abel9Eric Klann10Center for Neural Science, New York University, New York, NY, USACenter for Neural Science, New York University, New York, NY, USACenter for Neural Science, New York University, New York, NY, USACenter for Neural Science, New York University, New York, NY, USACenter for Neural Science, New York University, New York, NY, USACenter for Neural Science, New York University, New York, NY, USACenter for Neural Science, New York University, New York, NY, USACenter for Neural Science, New York University, New York, NY, USADepartment of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USACenter for Neural Science, New York University, New York, NY, USA; NYU Neuroscience Institute, New York University School of Medicine, New York, NY, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723016819CP: NeuroscienceCP: Molecular biology |
| spellingShingle | 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 The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation Cell Reports CP: Neuroscience CP: Molecular biology |
| title | The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation |
| title_full | The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation |
| title_fullStr | The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation |
| title_full_unstemmed | The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation |
| title_short | The integrated stress response effector GADD34 is repurposed by neurons to promote stimulus-induced translation |
| title_sort | integrated stress response effector gadd34 is repurposed by neurons to promote stimulus induced translation |
| topic | CP: Neuroscience CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723016819 |
| work_keys_str_mv | AT mauriciomoliveira theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT muhanedmohamed theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT megankelder theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT keylinbanegasmorales theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT maggiemamcarz theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT emilyhlu theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT elaangolhan theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT nishikanavrange theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT snehajyotichatterjee theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT tedabel theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT ericklann theintegratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT mauriciomoliveira integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT muhanedmohamed integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT megankelder integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT keylinbanegasmorales integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT maggiemamcarz integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT emilyhlu integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT elaangolhan integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT nishikanavrange integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT snehajyotichatterjee integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT tedabel integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation AT ericklann integratedstressresponseeffectorgadd34isrepurposedbyneuronstopromotestimulusinducedtranslation |