ArticleJournal of neuroscience research2010
Intracellular calcium and calmodulin link brain-derived neurotrophic factor to p70S6 kinase phosphorylation and dendritic protein synthesis.
Article in Journal of neuroscience research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
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- Carbamazepine Restores Neuronal Signaling, Protein Synthesis, and Cognitive Function in a Mouse Model of Fragile X Syndrome.International journal of molecular sciences · 2020Article
- Transcriptome signature analysis repurposes trifluoperazine for the treatment of fragile X syndrome in mouse model.Communications biology · 2020Article
- Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-BclxOncotarget · 2018Article
- Brain-Derived Neurotrophic Factor Increases Synaptic Protein Levels via the MAPK/Erk Signaling Pathway and Nrf2/Trx Axis Following the Transplantation of Neural Stem Cells in a Rat Model of Traumatic Brain Injury.Neurochemical research · 2017Article
- Article
- Differential Effects of 3rd Trimester-Equivalent Binge Ethanol and Tobacco-Specific Nitrosamine Ketone Exposures on Brain Insulin Signaling in Adolescence.Journal of diabetes and related disorders · 2016Article
- Reinstating aberrant mTORC1 activity in Huntington's disease mice improves disease phenotypes.Neuron · 2015Article
- From FMRP function to potential therapies for fragile X syndrome.Neurochemical research · 2014Review
- Estrogen Regulates Protein Synthesis and Actin Polymerization in Hippocampal Neurons through Different Molecular Mechanisms.Frontiers in endocrinology · 2014Article
- Calpain-2-mediated PTEN degradation contributes to BDNF-induced stimulation of dendritic protein synthesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Dendritic protein synthesis in the normal and diseased brain.Neuroscience · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway plays an important role in brain-derived neurotrophic factor (BDNF)-mediated protein synthesis and neuroplasticity. Although many aspects of neuronal function are regulated by intracellular calcium ([Ca(2+)](i)) and calmodulin (CaM), their functions in BDNF-induced phosphorylation of p70S6K and protein synthesis are largely unknown. Here, we report that BDNF, via TrkB-dependent activation of mTOR, induces sustained phosphorylation of p70S6K at Thr389 and Thr421/Ser424. BDNF-induced phosphorylation at Thr389 was dependent on PI3 kinase but independent of ERK-MAPK. The previously identified MAPK phosphorylation site at Thr421/Ser424 required both PI3K and MAPK in BDNF-stimulated neurons. Furthermore, we found that the reduction in [Ca(2+)](i), but not extracellular calcium, blocked the BDNF-induced phosphorylation of p70S6K at both sites. Inhibition of CaM by W13 also blocked p70S6K phosphorylation. In correlation, W13 inhibited BDNF-induced local dendritic protein synthesis. Interestingly, sustained elevation of [Ca(2+)](i) by membrane depolarization antagonized the BDNF-induced p70S6K phosphorylation. Finally, the BDNF-induced p70S6K phosphorylation did not require the increase of calcium level through either extracellular influx or PLC-mediated intracellular calcium release. Collectively, these results indicate that the basal level of intracellular calcium gates BDNF-induced activation of p70S6K and protein synthesis through CaM. (c) 2009 Wiley-Liss, Inc.
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