Abstract
A single second messenger, calcium, controls gene expression triggered by neuronal activity1,2, and the spatial properties of calcium signals determine the type of transcriptional response3. Nuclear calcium is a central regulator of transcription3,4,5, though synaptic activity may elicit calcium transients that are confined to a space near the site of entry6,7,8. Here we show that a calcium pool in the immediate vicinity of synaptic NMDA receptors is the on switch for extracellular signal-regulated kinase (ERK1/2)-mediated synapse-to-nucleus signaling; this signal propagates to the nucleus independently of global increases in calcium concentration, stimulates SRE-dependent gene expression and prolongs the transcriptionally active state of CREB following brief synaptic stimuli.
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Acknowledgements
We thank F. McKeon for the expression vector for NFAT4-GFP. This work was supported by the MRC, Dunhill Medical Trust, The Royal College of Surgeons of England, the Sackler Medical Research Centre and Clare College, Cambridge.
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Hardingham, G., Arnold, F. & Bading, H. A calcium microdomain near NMDA receptors: on switch for ERK-dependent synapse-to-nucleus communication. Nat Neurosci 4, 565–566 (2001). https://doi.org/10.1038/88380
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DOI: https://doi.org/10.1038/88380
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