ArticleThe Journal of biological chemistry2013
Nuclear calcium signaling regulates nuclear export of a subset of class IIa histone deacetylases following synaptic activity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 88 citations in OpenAlex.
- Restoring Neural Homeostasis via Class II HDAC Modulation: Mechanistic Insights and Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Advances in mitochondria-nucleus crosstalk in septic cardiomyopathy.Cell biology and toxicology · 2025Review
- N-terminal oligomerization drives HDAC4 nuclear condensation and neurodevelopmental dysfunction inOpen biology · 2025Article
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- VEGFD signaling balances stability and activity-dependent structural plasticity of dendrites.Cellular and molecular life sciences : CMLS · 2024Article
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- Using Human-Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential.Signal transduction and targeted therapy · 2023Review
- Neuronal nuclear calcium signaling suppression of microglial reactivity is mediated by osteoprotegerin after traumatic brain injury.Journal of neuroinflammation · 2022Article
- Role of Epigenetic Mechanisms in Chronic Pain.Cells · 2022Review
- Role of Altered Expression, Activity and Sub-cellular Distribution of Various Histone Deacetylases (HDACs) in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.Cellular and molecular neurobiology · 2022Article
- Organic anion transporter 1 is an HDAC4-regulated mediator of nociceptive hypersensitivity in mice.Nature communications · 2022Article
- Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity.Frontiers in bioengineering and biotechnology · 2022Article
- Electrophysiological- and Neuropharmacological-Based Benchmarking of Human Induced Pluripotent Stem Cell-Derived and Primary Rodent Neurons.Stem cell reviews and reports · 2022Article
- Histone deacetylases modulate resistance to the therapy in lung cancer.Frontiers in genetics · 2022Review
- Npas4 regulates medium spiny neuron physiology and gates cocaine-induced hyperlocomotion.EMBO reports · 2021Article
- Neuronal activity regulates the nuclear proteome to promote activity-dependent transcription.The Journal of cell biology · 2021Article
- The role of nuclear Ca2+ in maintaining neuronal homeostasis and brain health.Journal of cell science · 2021Review
- The nAChR Chaperone TMEM35a (NACHO) Contributes to the Development of Hyperalgesia in Mice.Neuroscience · 2021Article
- Increased Abundance of Nuclear HDAC4 Impairs Neuronal Development and Long-Term Memory.Frontiers in molecular neuroscience · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In neurons, dynamic changes in the subcellular localization of histone deacetylases (HDACs) are thought to contribute to signal-regulated gene expression. Here we show that in mouse hippocampal neurons, synaptic activity-dependent nucleo-cytoplasmic shuttling is a common feature of all members of class IIa HDACs, which distinguishes them from other classes of HDACs. Nuclear calcium, a key regulator in neuronal gene expression, is required for the nuclear export of a subset of class IIa HDACs. We found that inhibition of nuclear calcium signaling using CaMBP4 or increasing the nuclear calcium buffering capacity by means of expression of a nuclear targeted version of parvalbumin (PV.NLS-mC) led to a build-up of HDAC4 and HDAC5 in the cell nucleus, which in the case of PV.NLS-mC can be reversed by nuclear calcium transients triggered by bursts of action potential firing. A similar nuclear accumulation of HDAC4 and HDAC5 was observed in vivo in the mouse hippocampus following stereotaxic delivery of recombinant adeno-associated viruses expressing either CaMBP4 or PV.NLS-mC. The modulation of HDAC4 activity either by RNA interference-mediated reduction of HDAC4 protein levels or by expression of a constitutively nuclear localized mutant of HDAC4 leads to changes in the mRNA levels of several nuclear calcium-regulated genes with known functions in acquired neuroprotection (atf3, serpinb2), memory consolidation (homer1, arc), and the development of chronic pain (ptgs2, c1qc). These results identify nuclear calcium as a regulator of nuclear export of HDAC4 and HDAC5. The reduction of nuclear localized HDACs represents a novel transcription-promoting pathway stimulated by nuclear calcium.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.