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• W2000305419 endingPage "37609" @default.
• W2000305419 startingPage "37594" @default.
• W2000305419 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." @default.
• W2000305419 created "2016-06-24" @default.
• W2000305419 creator A5001777124 @default.
• W2000305419 creator A5004330439 @default.
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• W2000305419 creator A5053489094 @default.
• W2000305419 creator A5070992833 @default.
• W2000305419 creator A5082468653 @default.
• W2000305419 date "2012-11-01" @default.
• W2000305419 modified "2023-10-14" @default.
• W2000305419 title "Distinct Activation Properties of the Nuclear Factor of Activated T-cells (NFAT) Isoforms NFATc3 and NFATc4 in Neurons" @default.
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• W2000305419 doi "https://doi.org/10.1074/jbc.m112.365197" @default.
• W2000305419 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3488037" @default.
• W2000305419 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22977251" @default.
• W2000305419 hasPublicationYear "2012" @default.
• W2000305419 type Work @default.
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