L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-10

AUTHORS

Isabella A. Graef, Paul G. Mermelstein, Kryn Stankunas, Joel R. Neilson, Karl Deisseroth, Richard W. Tsien, Gerald R. Crabtree

ABSTRACT

The molecular basis of learning and memory has been the object of several recent advances, which have focused attention on calcium-regulated pathways controlling transcription. One of the molecules implicated by pharmacological, biochemical and genetic approaches is the calcium/calmodulin-regulated phosphatase, calcineurin1,2,3,4,5. In lymphocytes, calcineurin responds to specific calcium signals and regulates expression of several immediate early genes by controlling the nuclear import of the NF-ATc family of transcription factors6,7,8,9. Here we show that NF-ATc4/NF-AT3 (ref. 10) in hippocampal neurons can rapidly translocate from cytoplasm to nucleus and activate NF-AT-dependent transcription in response to electrical activity or potassium depolarization. The calcineurin-mediated translocation is critically dependent on calcium entry through L-type voltage-gated calcium channels. GSK-3 can phosphorylate NF-ATc4, promoting its export from the nucleus and antagonizing NF-ATc4-dependent transcription. Furthermore, we show that induction of the inositol 1,4,5-trisphosphate receptor type 1 is controlled by the calcium/calcineurin/NF-ATc pathway. This provides a new perspective on the function of calcineurin in the central nervous system and indicates that NF-AT-mediated gene expression may be involved in the induction of hippocampal synaptic plasticity and memory formation. More... »

PAGES

703-708

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/44378

DOI

http://dx.doi.org/10.1038/44378

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023364448

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10537109


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