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

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.

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