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Balanced interactions of calcineurin with AKAP79 regulate Ca2+-calcineurin-NFAT signaling.

Authors: Li, Huiming  Pink, Matthew D  Murphy, Jonathan G  Stein, Alexander  Dell'Acqua, Mark L  Hogan, Patrick G 
Citation: Li H, etal., Nat Struct Mol Biol. 2012 Feb 19;19(3):337-45. doi: 10.1038/nsmb.2238.
Pubmed: (View Article at PubMed) PMID:22343722
DOI: Full-text: DOI:10.1038/nsmb.2238

In hippocampal neurons, the scaffold protein AKAP79 recruits the phosphatase calcineurin to L-type Ca(2+) channels and couples Ca(2+) influx to activation of calcineurin and of its substrate, the transcription factor NFAT. Here we show that an IAIIIT anchoring site in human AKAP79 binds the same surface of calcineurin as the PxIxIT recognition peptide of NFAT, albeit more strongly. A modest decrease in calcineurin-AKAP affinity due to an altered anchoring sequence is compatible with NFAT activation, whereas a further decrease impairs activation. Counterintuitively, increasing calcineurin-AKAP affinity increases recruitment of calcineurin to the scaffold but impairs NFAT activation; this is probably due to both slower release of active calcineurin from the scaffold and sequestration of active calcineurin by 'decoy' AKAP sites. We propose that calcineurin-AKAP79 scaffolding promotes NFAT signaling by balancing strong recruitment of calcineurin with its efficient release to communicate with NFAT.

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CRRD Object Information
CRRD ID: 13507305
Created: 2018-02-28
Species: All species
Last Modified: 2018-02-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.