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| L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons |
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| Author(s): Graef IA, Mermelstein PG, Stankunas K, Neilson JR, Deisseroth K, Tsien RW, Crabtree GR |
| Source: NATURE Volume: 401 Issue: 6754 Pages: 703-708 Published: OCT 14 1999 |
| Times Cited: 232 References: 30 |
| 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, calcineurin(1-5). 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 factors(6-9). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Crabtree, GR (reprint author), Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Pathol, 300 Pasteur Dr, Stanford, CA 94305 USA |
Addresses:
1. Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Pathol, Stanford, CA 94305 USA
2. Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA
3. Stanford Univ, Beckman Ctr Mol & Genet Med, Sch Med, Dept Cellular & Mol Physiol, Stanford, CA 94305 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 247EJ |
| ISSN: 0028-0836 |
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