Cited by 249Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersPI3K/AKT/mTOR signaling in cancer

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Roles of Glutamate Receptors and the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Activity-dependent Dendritic Protein Synthesis in Hippocampal Neurons

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Gong, Ruomu, Park, Chang Sin, Abbassi, Nima Rezaei, Tang, Shao-Jun·2006·Journal of Biological Chemistry

DOI 10.1074/jbc.m512524200

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Abstract

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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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)
DOI: 10.1074/jbc.m512524200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5187 d)
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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Roles of Glutamate Receptors and the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Activity-dependent Dendritic Protein Synthesis in Hippocampal Neurons

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