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Brain-Derived Neurotrophic Factor Activation of CaM-Kinase Kinase via Transient Receptor Potential Canonical Channels Induces the Translation and Synaptic Incorporation of GluA1-Containing Calcium-Permeable AMPA Receptors
Open accessAbstract
Glutamatergic synapses in early postnatal development transiently express calcium-permeable AMPA receptors (CP-AMPARs). Although these GluA2-lacking receptors are essential and are elevated in response to brain-derived neurotrophic factor (BDNF), little is known regarding molecular mechanisms that govern their expression and synaptic insertion. Here we show that BDNF-induced GluA1 translation in rat primary hippocampal neurons requires the activation of mammalian target of rapamycin (mTOR) via calcium calmodulin-dependent protein kinase kinase (CaMKK). Specifically, BDNF-mediated phosphorylation of threonine 308 (T308) in AKT, a known substrate of CaMKK and an upstream activator of mTOR-dependent translation, was prevented by (1) pharmacological inhibition of CaMKK with STO-609, (2) overexpression of a dominant-negative CaMKK, or (3) short hairpin-mediated knockdown of CaMKK. GluA1 surface expression induced by BDNF, as assessed by immunocytochemistry using an extracellular N-terminal GluA1 antibody or by surface biotinylation, was impaired following knockdown of CaMKK or treatment with STO-609. Activation of CaMKK by BDNF requires transient receptor potential canonical (TRPC) channels as SKF-96365, but not the NMDA receptor antagonist d-APV, prevented BDNF-induced GluA1 surface expression as well as phosphorylation of CaMKI, AKT(T308), and mTOR. Using siRNA we confirmed the involvement of TRPC5 and TRPC6 subunits in BDNF-induced AKT(T308) phosphorylation. The BDNF-induced increase in mEPSC was blocked by IEM-1460, a selected antagonist of CP-AMPARs, as well as by the specific repression of acute GluA1 translation via siRNA to GluA1 but not GluA2. Together these data support the conclusion that newly synthesized GluA1 subunits, induced by BDNF, are readily incorporated into synapses where they enhance the expression of CP-AMPARs and synaptic strength.
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“BDNF has been shown to increase α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) responses by enhancing AMPA receptor translation and cell surface expression (Caldeira et al., 2007; Fortin et al., 2012).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Fortin et al., 2012
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Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
Mechanism of activation of protein kinase B by insulin and IGF‐1.
Alessi, D. R., Andjelković, M., Caudwell, B., Cron, P. D., MORRICE, N. A., Cohen, P., & Hemmings, B. A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01045.x · Cited by 3,014
Alessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 2,874
AMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588
Neurotrophin signal transduction in the nervous system
Kaplan, D. R., & Miller, F. D. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00092-1 · Cited by 1,944
Neurotrophins as synaptic modulators
Poo, M.-M. (2001) · Nature Reviews Neuroscience · doi:10.1038/35049004 · Cited by 1,775
SUnSET, a nonradioactive method to monitor protein synthesis
Schmidt, E. K., Clavarino, G., Ceppi, M., & Pierre, P. (2009) · Nature Methods · doi:10.1038/nmeth.1314 · Cited by 1,706
Self-citationRNA editing in brain controls a determinant of ion flow in glutamate-gated channels
Sommer, B., Köhler, M., Sprengel, R., & Seeburg, P. H. (1991) · Cell · doi:10.1016/0092-8674(91)90568-j · Cited by 1,517
Ca2 + Permeability of KA-AMPA—Gated Glutamate Receptor Channels Depends on Subunit Composition
Hollmann, M., Hartley, M., & Heinemann, S. F. (1991) · Science · doi:10.1126/science.1709304 · Cited by 1,450
BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis
Bramham, C. R., & Messaoudi, E. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.003 · Cited by 1,193
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Research works printed but not linked: 1
- Seeburg PH Higuchi M Sprengel R RNA editing of brain glutamate receptor channels: mechanism and physiology Brain Res Brain Res Rev 1998 26 217 229 9651532
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Amen, A. M., Pham, D. L., & Meffert, M. K. (2015) · Springer eBooks · doi:10.1007/978-3-319-25124-0_14 · Cited by 3
Wang, Y., Li, Y., Chen, D., Tu, L., Hou, Q., & Wang, S. (2016) · Neuroreport · doi:10.1097/wnr.0000000000000659 · Cited by 3
Receptors | Neurotrophin Receptor Signaling
Kraemer, B. R., & Carter, B. D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819460-7.00310-8 · Cited by 3
Zhao, D.-P., Lei, X., Wang, Y., Ao, X., Zhao, C.-Y., Xu, Y., Zhang, Y., Liu, G., Geng, F., Xu, H., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.971385 · Cited by 2
Dubourg, A., Harnois, T., Cousin, L., Constantin, B., & Bourmeyster, N. (2024) · Cancers · doi:10.3390/cancers16162791 · Cited by 1
Aicardi, G. (2012) · Rejuvenation Research · doi:10.1089/rej.2012.1375 · Cited by 1
RetractedAicardi, G. (2013) · Rejuvenation Research · doi:10.1089/rej.2013.1448 · Cited by 1
Activity-dependent changes in the dendritic distribution of hnRNP K : functional implications
de Morais, E. C. C. (2014) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Examination of mechanisms underlying the effect of single-session exercise on cortical plasticity
Thacker, J. S. (2018) · UWSpace (University of Waterloo)
Proteomic Tools to Study the Effect of BDNF on De Novo Protein Synthesis
Bowling, H. L., & Klann, E. (2018) · Neuromethods · doi:10.1007/7657_2018_16
Navarro‐Lobato, I., Masmudi‐Martín, M., López‐Aranda, M. F., Lopez-Tellez, J. F., Delgado, G., Granados‐Durán, P., Gaona‐Romero, C., Carretero‐Rey, M., Posadas, S. J., Quirós-Ortega, M. E., et al. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.389301
Phasuk, S., Pairojana, T., Suresh, P., Yang, C.-H., Roytrakul, S., Huang, S.-P., Chen, C., Pakaprot, N., Chompoopong, S., Nudmamud‐Thanoi, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14121482
Glasgow, S. D., Wong, E. W., Thompson‐Steckel, G., Marçal, N., Séguéla, P., Ruthazer, E. S., & Kennedy, T. E. (2020) · Figshare · doi:10.6084/m9.figshare.12096426
Hu, F. X., Liu, Z., Min, X., Zhang, K., Zhao, H., Liu, W., Tao, Y., Jia, Q., Gao, Y., Meng, X., et al. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110818
Evans, H. T., Kalavai, S. V., Wu, V., Polavarapu, A., Balamoti, E., Liu, W., Mosto, O., Adler, D. I., Jain, V., Denil, E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.12.699151
Dual regulatory roles of CPT1C in chronic stress-induced depression-related outcomes
Tian, D., Xia, Z., Wang, S.-Y., Cao, T., Pan, Y., Zhao, Y., Zheng, L., Wei, B.-J., Yang, S.-W., Chen, W., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03516-4
Jia, S., Rybalchenko, N., Paundralingga, O. T. K., Appiah, C. B., Farmer, G. E., & Cunningham, J. T. (2026) · Journal of Neurophysiology · doi:10.1152/jn.00265.2026
Distinct roles of AMPA receptor subunits as potential therapeutic targets in Alzheimer’s disease
Seo, J., Kim, K., & Park, M. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108394
Li, Y., Liao, Y., Zhang, S., Xu, C., Lan, R., Zhao, P., Liu, R., Song, Y., & Zhang, X. (2026) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2026.1923815
Metadata
- Authors
- Fortin, D. A., Srivastava, T., Dwarakanath, D., Pierre, P., Nygaard, S., Derkach, V. A., & Soderling, T. R.
- Affiliations
- Oregon Health & Science University (US)
- Aix-Marseille Université (FR)
- Corresponding author
- Fortin, D. A.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-06-13
- Volume
- 32
- Issue
- 24
- Pages
- 8127-8137
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3390208
- OpenAlex
- W1965868120
- Cited by
- 120
- References
- 87
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2023: 8 · 2022: 10 · 2021: 9 · 2020: 7 · 2019: 2 · 2018: 9 · 2017: 12 · 2016: 8 · 2015: 8 · 2014: 15 · 2013: 19 · 2012: 3
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS027037, NS027037)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- brain-derived neurotrophic factor, calcium-permeable AMPA receptors, CaMKK, mTOR signaling, Akt phosphorylation, TRPC5, TRPC6, TRPC channels, glutamatergic synapses, hippocampal neurons, STO-609
- MeSH terms
- Adamantane, Animals, Benzimidazoles, Calcium Channel Blockers, Enzyme Inhibitors, Female, Hippocampus, Imidazoles, Male, Neurons, 2-Amino-5-phosphonovalerate, Rats, Sprague-Dawley, Receptors, AMPA, Excitatory Amino Acid Antagonists, Brain-Derived Neurotrophic Factor, RNA, Small Interfering, TRPC Cation Channels, Rats, Naphthalimides, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Miniature Postsynaptic Potentials, Gene Knockdown Techniques, TOR Serine-Threonine Kinases, Primary Cell Culture
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