Tomida-EMBO-J-2003-NFAT-translocation.omex
title: Calcium-induced NFAT translocation (Tomida et al., EMBO J, 2003)
abstract: Model of the kinetics of dephosphorylation and translocation of NFAT. The model captures the rapid Ca(2+)-dependent dephosphorylation of NFAT and its slow rephosphorylation and nuclear transport which govern the lifetime of NFAT in the cytoplasm.
keyword: Calcium Signaling
keyword: Cricetinae
keyword: NFATC Transcription Factors
description: 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.
has taxon: Homo sapiens
  identifier: http://identifiers.org/taxonomy/9606
encodes: calcineurin-NFAT signaling cascade
  identifier: GO:0033173
encodes: JURKAT cell
  identifier: BTO:0000661
is: biomodels.db:BIOMD0000000678
  identifier: biomodels.db:BIOMD0000000678
creator: Taichiro Tomida
creator: Kenzo Hirose
creator: Azusa Takizawa
creator: Futoshi Shibasaki
creator: Masamitsu Iino
contributor: Vijayalakshmi Chelliah
contributor: Jonathan Karr
  account name: https://orcid.org/0000-0002-2605-5080
  identifier: orcid:0000-0002-2605-5080
contributor: Ryann Jordan
is described by: Taichiro Tomida, Kenzo Hirose, Azusa Takizawa, Futoshi Shibasaki & Masamitsu Iino. NFAT functions as a working memory of Ca2+ signals in decoding Ca2+ oscillation. EMBO J 22, 15 (2003): 3825-3832.
  identifier: cdg381
license: CC0-1.0
  identifier: spdx:CC0-1.0
created:
  W3 CDTF: 2003-08-01
modified:
  W3 CDTF: 2021-07-21

Figure 3c
is: Figure 3c
  identifier: cdg381