Departmental Papers (BE)

Document Type

Journal Article

Date of this Version

4-2016

Publication Source

Cell Systems

Volume

2

Issue

4

Start Page

283

Last Page

288

DOI

10.1016/j.cels.2016.03.010

Abstract

It is known that the calcium-dependent transcription factor NFAT initiates transcription in response to pulsatile loads of calcium signal. However, the relative contributions of calcium oscillation frequency, amplitude, and duty cycle to transcriptional activity remain unclear. Here, we engineer HeLa cells to permit optogenetic control of intracellular calcium concentration using programmable LED arrays. This approach allows us to generate calcium oscillations of constant peak amplitude, in which frequency is varied while holding duty cycle constant, or vice versa. Using this setup and mathematical modeling, we show that NFAT transcriptional activity depends more on duty cycle, defined as the proportion of the integrated calcium concentration over the oscillation period, than on frequency alone. This demonstrates that NFAT acts primarily as a signal integrator of cumulative load rather than a frequency-selective decoder. This approach resolves a fundamental question in calcium encoding and demonstrates the value of optogenetics for isolating individual dynamical components of larger signaling behaviors.

Copyright/Permission Statement

CC-BY-NC-ND

Embargo Date

4-27-2017

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Date Posted: 28 April 2016

This document has been peer reviewed.