Calcineurin/NFAT Signaling in Development and Function of the Nervous System
The four genes that encode the cytoplasmic subunits of NFAT-transcription complexes (NFATc proteins) are both transcription factors and signaling molecules. Calcium stimuli in neurons lead to the activation of calcineurin (CaN) phosphatase activity and the rapid dephosphorylation of NFATc proteins. Once in the nucleus, these proteins assemble on DNA with nuclear partner proteins (NFATns) and form active transcription complexes. This mechanism allows NFAT complexes to function as coincidence detectors and signal integrators. The specificity of Ca2+ signaling at a transcriptional level might arise from combinatorial assembly of diverse NFAT complexes. Rapid export from the nucleus following rephosphorylation by GSK3 insulates NFAT transcription from transient Ca2+ fluxes and plays a critical role in the decoding of Ca2+ signals. Recent studies have indicated that NFAT signaling and transcriptional control play roles in axon outgrowth, synaptogenesis, memory formation and possibly in laying down common tracks for nerves and vessels during development. Genetic studies in mice and humans indicate that NFAT signaling might play a role in schizophrenia and the developmental defects of Down syndrome. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.
