Editors' ChoiceCalcium signaling

Calcium signaling: Regulation of Gene Expression by Neuronal Calcium

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Science's STKE  19 Oct 1999:
Vol. 1999, Issue 4, pp. tw2
DOI: 10.1126/stke.1999.4.tw2

The control of gene expression by calcium and the NF-AT family of transcription factors may not just occur in lymphocytes. Graef et al. now report a similar pathway in neurons. Electrical activity or depolarization of hippocampal neurons stimulated the entry of calcium through L-type voltage-gated channels. This event resulted in a calcineurin-dependent dephosphorylation of the NF-ATc4 transcription factor and its subsequent relocalization to the nucleus. The serine-threonine kinase GSK-3 appeared to do just the opposite: The enzyme inhibited transcription in neurons by phosphorylating NF-ATc4. This modification promoted the nuclear export of the transcription factor. The authors suggest that this calcium-dependent mechanism of transcriptional control may be linked to the expression of the inositol 1,4,5-triphosphate receptor and regulation of synaptic plasticity in such neurons.

Graef, I.A., Mermelstein, P.G., Stankunas, K., Nellson, J.R., Deisseroth, K., Tsien, R.W., and Crabtree, G. R. (1999) L-type calcium channels and GSK-3 regulate the activity of NF-Atc4 in hippocampal neurons. Nature 401: 703-708.[Online Journal]

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