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Tomida2003 - Calcium Oscillatory-induced translocation of nuclear factor of activated T cells


ABSTRACT: Tomida2003 - NFAT functions Calcium Oscillation This model is described in the article: NFAT functions as a working memory of Ca2+ signals in decoding Ca2+ oscillation. Tomida T, Hirose K, Takizawa A, Shibasaki F, Iino M. EMBO J. 2003 Aug; 22(15): 3825-3832 Abstract: Transcription by the nuclear factor of activated T cells (NFAT) is regulated by the frequency of Ca(2+) oscillation. However, why and how Ca(2+) oscillation regulates NFAT activity remain elusive. NFAT is dephosphorylated by Ca(2+)-dependent phosphatase calcineurin and translocates from the cytoplasm to the nucleus to initiate transcription. We analyzed the kinetics of dephosphorylation and translocation of NFAT. We show that Ca(2+)-dependent dephosphorylation proceeds rapidly, while the rephosphorylation and nuclear transport of NFAT proceed slowly. Therefore, after brief Ca(2+) stimulation, dephosphorylated NFAT has a lifetime of several minutes in the cytoplasm. Thus, Ca(2+) oscillation induces a build-up of dephosphorylated NFAT in the cytoplasm, allowing effective nuclear translocation, provided that the oscillation interval is shorter than the lifetime of dephosphorylated NFAT. We also show that Ca(2+) oscillation is more cost-effective in inducing the translocation of NFAT than continuous Ca(2+) signaling. Thus, the lifetime of dephosphorylated NFAT functions as a working memory of Ca(2+) signals and enables the control of NFAT nuclear translocation by the frequency of Ca(2+) oscillation at a reduced cost of Ca(2+) signaling. This model is hosted on BioModels Database and identified by: BIOMD0000000678. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Vijayalakshmi Chelliah  

PROVIDER: BIOMD0000000678 | BioModels | 2018-02-22

REPOSITORIES: BioModels

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NFAT functions as a working memory of Ca2+ signals in decoding Ca2+ oscillation.

Tomida Taichiro T   Hirose Kenzo K   Takizawa Azusa A   Shibasaki Futoshi F   Iino Masamitsu M  

The EMBO journal 20030801 15


Transcription by the nuclear factor of activated T cells (NFAT) is regulated by the frequency of Ca(2+) oscillation. However, why and how Ca(2+) oscillation regulates NFAT activity remain elusive. NFAT is dephosphorylated by Ca(2+)-dependent phosphatase calcineurin and translocates from the cytoplasm to the nucleus to initiate transcription. We analyzed the kinetics of dephosphorylation and translocation of NFAT. We show that Ca(2+)-dependent dephosphorylation proceeds rapidly, while the rephosp  ...[more]

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