The DOI matches its Crossref record; 59 of the 73 references it cites were found in a registry or an index.
Roles of Glutamate Receptors and the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Activity-dependent Dendritic Protein Synthesis in Hippocampal Neurons
Open accessAbstract
Local protein synthesis in neuronal dendrites is critical for synaptic plasticity. However, the signaling cascades that couple synaptic activation to dendritic protein synthesis remain elusive. The purpose of this study is to determine the role of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling in regulating dendritic protein synthesis in live neurons. We first characterized the involvement of various subtypes of glutamate receptors and the mTOR kinase in regulating dendritic synthesis of a green fluorescent protein (GFP) reporter controlled by alphaCaMKII 5' and 3' untranslated regions in cultured hippocampal neurons. Specific antagonists of N-methyl-d-aspartic acid (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and metabotropic glutamate receptors abolished glutamate-induced dendritic GFP synthesis, whereas agonists of NMDA and metabotropic but not AMPA glutamate receptors activated GFP synthesis in dendrites. Inhibitions of the mTOR signaling, as well as its upstream activators, phosphatidylinositol 3-kinase and AKT, blocked NMDA receptor-dependent dendritic GFP synthesis. Conversely, activation of mTOR signaling stimulated dendritic GFP synthesis. In addition, we also found that inhibition of the mTOR kinase blocked dendritic synthesis of the endogenous alphaCaMKII and MAP2 proteins induced by tetanic stimulations in hippocampal slices. These results identify critical roles of NMDA receptors and the mTOR signaling pathway for control of synaptic activity-induced dendritic protein synthesis in hippocampal neurons.
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“Activation of mTOR has been functionally linked with local protein synthesis, such as the presynaptically as synapsin I (SYN1), as well as cytoskeletal proteins, such as the activity-regulated cytoskeletal-associated protein (ARC) [15,24,25].”
From The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes (2023) · cites this paper as [25]
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Items 201–227 of 227
Epitranscriptome and FMRP Regulated mRNA Translation
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BackgroundSignaling Pathways Relevant to Cognition-Enhancing Drug Targets
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“Activation of NMDAR and mGluR modulates activity-dependent dendritic synthesis through mTOR activity in hippocampal neurons (Gong et al. 2006).”
BackgroundIs Nuclear mTOR Relevant for Neuronal Dysfunction?
Kumari, S., Pagano, R., Orzoł, K., & Jaworski, J. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70528
“In neurons, both complexes are additionally regulated by neurotransmitter signaling and neuronal activity (Page et al. 2006; Hou and Klann 2004; Gong et al. 2006; Lenz and Avruch 2005; Schicknick et al. 2008; Carroll et al. 2006). mTORC1 is activated by the small GTPases Ras homolog enriched in…”
Activation of AMPK/OPA1 pathway alleviates traumatic brain damage by regulating mitophagy
Wei, H., Liao, J., Gao, W., & He, X. (2025) · Acta Cirurgica Brasileira · doi:10.1590/acb406925 · Cited by 1
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“Likewise, glutamate transmission evoked with high potassium or glutamate agonists leads to an APV-sensitive increase in translation in processes of cultured hippocampal neurons [61].”
Intrahippocampal glutamine administration inhibits mTORC1 signaling and impairs long-term memoryPreprint
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“…infusion impairs long-term spatial memory Previous genetic and pharmacological studies have shown that mTORC1 signaling is critical for hippocampus-dependent longterm memory formation (Kelleher et al. 2004; Dash et al. 2006; Gong et al. 2006; Swiech et al. 2008; Costa-Mattioli et al. 2009).”
BackgroundResultInfluentialMoniTORing neuronal excitability at the synapse
Kepert, I., & Kiebler, M. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201304183 · Cited by 1
Ankarali, S., Beyazçiçek, E., Ankarali, H., & Demir, Ş. (2016) · doi:10.21673/aktbd.99419 · Cited by 1
“As mTOR can be activated by glutamate receptor stimulation (39,40), it is not surprising that the initial mTOR activation occurs with status epilepticus, which causes massive glutamate release (16,41).”
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Molle, K. D. (2006) · edoc (University of Basel) · doi:10.5451/unibas-004670272 · Cited by 1
mTORC2-Na v 1.2 signaling drives early hyperexcitability in Alzheimer’s disease mouse model
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“…function and thereby contribute to hyperexcitability, such as calcium/calmodulin protein kinase II (CaMKII) [80] are regulated by mTOR signaling [81] and are dysregulated in subjects with MCI [82], further warranting study of the mTORC2/Na v 1.2 interaction in contributing to early-stage AD…”
InfluentialPark, D.-H., Ahn, S.-Y., Kim, J., Choi, J.-W., Lee, S.-H., Kang, M.-J., Song, J.-M., & Suh, Y. H. (2025) · bioRxiv · doi:10.1038/s44319-026-00766-9
“Notably, mTOR has been shown to interact with G3BP1 (Prentzell et al, 2021; Schwarz et al, 2015) and is activated downstream of NMDAR signaling to promote dendritic and axonal protein synthesis (Gong et al, 2006; Wong et al, 2024).”
Naeini, S., Mesripour, A., & Hajhashemi, V. (2023) · Bulletin of Pharmaceutical Sciences. Assiut · doi:10.21608/bfsa.2023.218646.1785
“Additionally, the NMDA receptors influences and controls the mTOR pathway functioning 36 .”
BackgroundZimbelman, A. R., Wong, B., Murray, C. H., Wolf, M., & Stefanik, M. T. (2023) · bioRxiv · doi:10.1101/2023.04.02.535293
“Likewise, glutamate transmission evoked with high potassium or glutamate agonists leads to an APV-sensitive increase in translation in processes of cultured hippocampal neurons [57].”
BackgroundResultAbebe, E., Mengstie, M. A., Seid, M. A., & Dejenie, T. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1051235
Paterniti, I., Campolo, M., Casili, G., Lanza, M., Filippone, A., Cordaro, M., Ardizzone, A., Scuderi, S., Cuzzocrea, S., & Esposito, E. (2020) · doi:10.21203/rs.2.24093/v1
“Autophagy is a major player in the control of cell size, dendrite and axon outgrowth during brain development, and repair (7, 8).”
BackgroundGiannotti, G. (2016) · doi:10.13130/g-giannotti_phd2016-01-12
“TrkB enhancement resulted in a selective activation of the Akt-dependent pathway that, in turn, activated both mTOR and S6 phosphorylation (Gong et al., 2006), a canonical pathway known to be activated by BDNF 67 (Swiech et al., 2008) thereby promoting mRNA translation (Hoeffer and Klann, 2010).”
ROLE OF AUTOPHAGY IN NEURITE DEGENERATION IN VITRO
Yang, Y., Zheng, X., & Koike, T. (2012) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789814350457_0017
Mammalian target of rapamycin complexes
Querfurth, H. W., & Lee, H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-815868-5.00022-0
Şenay, O., Balcıoglu, Y., & İlnem, M. (2019) · Psychiatry and Behavioral Sciences · doi:10.5455/pbs.20180628062738
“140 hippocampal dendritic protein synthesis in mice neurons has been induced by the activation of glutamate receptors, particularly NMDA and metabotropic receptors (12).”
BackgroundPI3K Signaling and miRNA Regulation in Autism Spectrum Disorders
Kwok, S., Mellios, N., & Sur, M. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-391924-3.00033-8
Metadata
- Authors
- Gong, R., Park, C. S., Abbassi, N. R., & Tang, S.-J.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Tang, Shao-Jun
- ORCID
- Tang, Shao-Jun
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 281
- Issue
- 27
- Pages
- 18802-18815
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2064438779
- Cited by
- 249
- References
- 73
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 14 · 2020: 11 · 2019: 7 · 2018: 13 · 2017: 14 · 2016: 10 · 2015: 21 · 2014: 14 · 2013: 19 · 2012: 25
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- dendritic protein synthesis, glutamate receptors, mTOR signaling, NMDA receptor, AMPA receptors, metabotropic glutamate receptors, hippocampal neurons, synaptic plasticity, CaMKIIα, MAP2, phosphatidylinositol 3-kinase, Akt, tetanic stimulation, local translation
- MeSH terms
- Animals, Cells, Cultured, Dendrites, Hippocampus, Neurons, Protein Kinases, Synapses, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Calcium-Calmodulin-Dependent Protein Kinases, Genes, Reporter, Green Fluorescent Proteins, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, TOR Serine-Threonine Kinases
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