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NFAT functions as a working memory of Ca2+ signals in decoding Ca2+ oscillation
Taichiro Tomida1, Kenzo Hirose, Azusa Takizawa
1Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
The EMBO Journal
|July 26, 2003
Summary
Calcium (Ca2+) oscillation frequency controls nuclear factor of activated T cells (NFAT) transcription. The lifetime of dephosphorylated NFAT acts as a molecular memory, enabling frequency-dependent nuclear translocation and reducing signaling costs.
Area of Science:
- Molecular Biology
- Cell Signaling
- Immunology
Background:
- Nuclear factor of activated T cells (NFAT) transcription is regulated by calcium (Ca2+) oscillation frequency.
- The precise mechanisms by which Ca2+ oscillations control NFAT activity are not fully understood.
Purpose of the Study:
- To elucidate the kinetics of NFAT dephosphorylation and nuclear translocation.
- To understand how Ca2+ oscillation frequency regulates NFAT activity.
Main Methods:
- Analysis of NFAT dephosphorylation and translocation kinetics.
- Investigated the impact of Ca2+ stimulation patterns (oscillation vs. continuous) on NFAT.
- Quantified the lifetime of dephosphorylated NFAT in the cytoplasm.
Main Results:
- Ca2+-dependent dephosphorylation of NFAT is rapid, while rephosphorylation and nuclear transport are slow.
- Dephosphorylated NFAT has a cytoplasmic lifetime of several minutes after brief Ca2+ stimulation.
- Ca2+ oscillation leads to a build-up of dephosphorylated NFAT, promoting nuclear translocation if oscillation intervals are short.
- Ca2+ oscillation is more energy-efficient for NFAT translocation than continuous signaling.
Conclusions:
- The lifetime of dephosphorylated NFAT serves as a working memory for Ca2+ signals.
- NFAT nuclear translocation is controlled by Ca2+ oscillation frequency, leveraging this molecular memory.
- This mechanism allows for efficient and cost-effective regulation of NFAT-mediated transcription.