Dynamic Response Diversity of NFAT Isoforms in Individual Living Cells

Nissan Yissachar; Tali Sharar Fischler; Ariel A. Cohen; Shlomit Reich-Zeliger; Dor Russ; Eric Shifrut; Ziv Porat; Nir Friedman

doi:10.1016/j.molcel.2012.11.003

Dynamic Response Diversity of NFAT Isoforms in Individual Living Cells

Nissan Yissachar, Tali Sharar Fischler, Ariel A. Cohen, Shlomit Reich-Zeliger, Dor Russ, Eric Shifrut, Ziv Porat, Nir Friedman

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

Abstract

Processing of external information by mammalian cells often involves seemingly redundant isoforms of signaling molecules and transcription factors. Understanding the functional relevance of coexpressed isoforms that respond to the same signal and control a shared set of genes is still limited. Here we show, using imaging of individual living mammalian cells, that the closely related transcription factors NFAT1 and NFAT4 possess distinct nuclear localization dynamics in response to cell stimulation. NFAT4 shows a fast response, with rapid stochastic bursts of nuclear localization. Burst frequency grows with signal level, while response amplitude is fixed. In contrast, NFAT1 has a slow, continuous response, and its amplitude increases with signal level. These diverse dynamical features observed for single cells are translated into different impulse response strategies at the cell population level. We suggest that dynamic response diversity of seemingly redundant genes can provide cells with enhanced capabilities of temporal information processing.

Original language	English
Pages (from-to)	322-330
Number of pages	9
Journal	Molecular Cell
Volume	49
Issue number	2
DOIs	https://doi.org/10.1016/j.molcel.2012.11.003
State	Published - 24 Jan 2013
Externally published	Yes

Bibliographical note

Funding Information:
We are grateful to Israel Pecht and Arieh Licht for kindly providing reagents and for useful discussions and suggestions, Ezra Vadai for technical assistance, and Catherine Laplace for graphical assistance. We thank Uri Alon, Long Cai, Mike Fainzilber, and Yitzhak Pilpel for useful comments on the manuscript. This research was supported by the International Human Frontier Science Program Organization, the Yeda-Sela Center for Basic Research, the Planning and Budgeting Committee of the Israeli Council for Higher Education, and the European Union 7th Framework Programme as part of the NanoII Project, Grant Number 229289. N.F. is incumbent of the Pauline Recanati Career Development Chair.

Funding

We are grateful to Israel Pecht and Arieh Licht for kindly providing reagents and for useful discussions and suggestions, Ezra Vadai for technical assistance, and Catherine Laplace for graphical assistance. We thank Uri Alon, Long Cai, Mike Fainzilber, and Yitzhak Pilpel for useful comments on the manuscript. This research was supported by the International Human Frontier Science Program Organization, the Yeda-Sela Center for Basic Research, the Planning and Budgeting Committee of the Israeli Council for Higher Education, and the European Union 7th Framework Programme as part of the NanoII Project, Grant Number 229289. N.F. is incumbent of the Pauline Recanati Career Development Chair.

Funders	Funder number
Israeli Council for Higher Education
Yeda-Sela Center for Basic Research
Human Frontier Science Program
Seventh Framework Programme	229289

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10.1016/j.molcel.2012.11.003

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title = "Dynamic Response Diversity of NFAT Isoforms in Individual Living Cells",

abstract = "Processing of external information by mammalian cells often involves seemingly redundant isoforms of signaling molecules and transcription factors. Understanding the functional relevance of coexpressed isoforms that respond to the same signal and control a shared set of genes is still limited. Here we show, using imaging of individual living mammalian cells, that the closely related transcription factors NFAT1 and NFAT4 possess distinct nuclear localization dynamics in response to cell stimulation. NFAT4 shows a fast response, with rapid stochastic bursts of nuclear localization. Burst frequency grows with signal level, while response amplitude is fixed. In contrast, NFAT1 has a slow, continuous response, and its amplitude increases with signal level. These diverse dynamical features observed for single cells are translated into different impulse response strategies at the cell population level. We suggest that dynamic response diversity of seemingly redundant genes can provide cells with enhanced capabilities of temporal information processing.",

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Dynamic Response Diversity of NFAT Isoforms in Individual Living Cells

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