Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites
Open accessAbstract
In neurons, perisynaptic or dendritic translation is implicated in synapse-wide alterations of function and morphology triggered by neural activity. The molecular mechanisms controlling local translation activation, however, have yet to be elucidated. Here, we show that local protein synthesis and translational activation in neuronal dendrites are upregulated by brain-derived neurotrophic factor (BDNF) in a rapamycin and small interfering RNA specific for mammalian target of rapamycin (mTOR)-sensitive manner. In parallel, BDNF induced the phosphorylation of tuberin and the activation of mTOR in dendrites and the synaptoneurosome fraction. mTOR activation stimulated translation initiation processes involving both eIF4E/4E-binding protein ( 4EBP ) and p70S6 kinase/ribosomal S6 protein. BDNF induced phosphorylation of 4EBP in isolated dendrites. Moreover, local puff application of BDNF to dendrites triggered S6 phosphorylation in a restricted area. Taken together, these data indicate that mTOR-dependent translation activation is essential for the upregulation of local protein synthesis in neuronal dendrites.
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BDNF is a potent activator of mTOR signaling.
“Previous work has shown that BDNF is a potent activator of mTOR signaling (Jourdi et al., 2009; Takei et al., 2004; Slipczuk et al., 2009), and mTOR is a key integrator for many signaling pathways (see Costa-Mattioli and Monteggia, 2013).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Takei et al., 2004
BDNF reduces the pool of CYFIP1 repressing translation and concomitantly increases the amount of CYFIP1 recruited on the WRC.
“BDNF, a neurotrophin and synaptic plasticity-inducing factor, able to induce protein synthesis (Takei et al., 2004) and cytoskeleton rearrangements (Bramham, 2008), reduces the pool of CYFIP1 repressing translation and concomitantly increases the amount of CYFIP1 recruited on the WRC.”
From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Takei et al., 2004
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- Authors
- Takei, N., Inamura, N., Kawamura, M., Namba, H., Hara, K., Yonezawa, K., & Nawa, H.
- Affiliations
- Brain Research Institute, Niigata University (JP)
- Japan Science and Technology Agency (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-11-03
- Volume
- 24
- Issue
- 44
- Pages
- 9760-9769
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6730227
- OpenAlex
- W2074838566
- Cited by
- 442
- References
- 6
- Citations by year
- 2026: 16 · 2025: 12 · 2024: 13 · 2023: 13 · 2022: 23 · 2021: 24 · 2020: 26 · 2019: 15 · 2018: 22 · 2017: 25 · 2016: 24 · 2015: 24 · 2014: 27 · 2013: 29 · 2012: 23
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novartis Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain-derived neurotrophic factor, mTOR, local translation, dendritic protein synthesis, tuberin, 4E-BP, p70 S6 kinase, ribosomal protein S6, synaptic plasticity, dendrites, translational regulation
- MeSH terms
- Ras Homolog Enriched in Brain Protein, Tuberous Sclerosis Complex 2 Protein, Animals, Cells, Cultured, Cerebral Cortex, Dendrites, Gene Expression Regulation, Nerve Tissue Proteins, Neuronal Plasticity, Neuropeptides, Protein Kinases, Repressor Proteins, Synaptosomes, Protein Biosynthesis, Brain-Derived Neurotrophic Factor, Sirolimus, Monomeric GTP-Binding Proteins, Tumor Suppressor Proteins, RNA, Small Interfering, Rats, TOR Serine-Threonine Kinases
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