ArticleThe Journal of biological chemistry2012
Distinct activation properties of the nuclear factor of activated T-cells (NFAT) isoforms NFATc3 and NFATc4 in neurons.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Calcineurin/NFAT signaling in the temporal integration of Ca²⁺ stress in neurodegeneration.Cell death discovery · 2026Review
- DHA elongates the neuronal primary cilium through GPR40-mediated signaling.Frontiers in cell and developmental biology · 2026Article
- miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity.EMBO reports · 2024Article
- miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity.bioRxiv : the preprint server for biology · 2023Article
- Excitation-transcription coupling, neuronal gene expression and synaptic plasticity.Nature reviews. Neuroscience · 2023Review
- The alpha-synuclein oligomers activate nuclear factor of activated T-cell (NFAT) modulating synaptic homeostasis and apoptosis.Molecular medicine (Cambridge, Mass.) · 2023Article
- Targeting CaN/NFAT in Alzheimer's brain degeneration.Frontiers in immunology · 2023Review
- Primary biliary cholangitis: molecular pathogenesis perspectives and therapeutic potential of natural products.Frontiers in immunology · 2023Review
- Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3.Cell death and differentiation · 2022Article
- Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis.Journal of hepatology · 2021Article
- NFATc2-dependent epigenetic upregulation of CXCL14 is involved in the development of neuropathic pain induced by paclitaxel.Journal of neuroinflammation · 2020Article
- CaBiophysical journal · 2020Article
- Targeting Tyrosine kinases in Renal Cell Carcinoma: "New Bullets against Old Guys".International journal of molecular sciences · 2019Review
- Mitochondrial calcium signalling and neurodegenerative diseases.Neuronal signaling · 2018Review
- Nanoluciferase Reporter Gene System Directed by Tandemly Repeated Pseudo-Palindromic NFAT-Response Elements Facilitates Analysis of Biological Endpoint Effects of Cellular CaInternational journal of molecular sciences · 2018Article
- Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia.Frontiers in behavioral neuroscience · 2018Article
- Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Genetic Susceptibility to Bortezomib-Induced Peripheral Neuroropathy: Replication of the Reported Candidate Susceptibility Loci.Neurochemical research · 2017Article
- NFATc2 Modulates Microglial Activation in the AβPP/PS1 Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2017Article
- Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
The Ca(2+)/calcineurin-dependent transcription factor NFAT (nuclear factor of activated T-cells) is implicated in regulating dendritic and axonal development, synaptogenesis, and neuronal survival. Despite the increasing appreciation for the importance of NFAT-dependent transcription in the nervous system, the regulation and function of specific NFAT isoforms in neurons are poorly understood. Here, we compare the activation of NFATc3 and NFATc4 in hippocampal and dorsal root ganglion neurons following electrically evoked elevations of intracellular Ca(2+) concentration ([Ca(2+)](i)). We find that NFATc3 undergoes rapid dephosphorylation and nuclear translocation that are essentially complete within 20 min, although NFATc4 remains phosphorylated and localized to the cytosol, only exhibiting nuclear localization following prolonged (1-3 h) depolarization. Knocking down NFATc3, but not NFATc4, strongly diminished NFAT-mediated transcription induced by mild depolarization in neurons. By analyzing NFATc3/NFATc4 chimeras, we find that the region containing the serine-rich region-1 (SRR1) mildly affects initial NFAT translocation, although the region containing the serine-proline repeats is critical for determining the magnitude of NFAT activation and nuclear localization upon depolarization. Knockdown of glycogen synthase kinase 3β (GSK3β) significantly increased the depolarization-induced nuclear localization of NFATc4. In contrast, inhibition of p38 or mammalian target of rapamycin (mTOR) kinases had no significant effect on nuclear import of NFATc4. Thus, electrically evoked [Ca(2+)](i) elevation in neurons rapidly and strongly activates NFATc3, whereas activation of NFATc4 requires a coincident increase in [Ca(2+)](i) and suppression of GSK3β, with differences in the serine-proline-containing region giving rise to these distinct activation properties of NFATc3 and NFATc4.
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Registered trials
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.