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G3 (Bethesda). 2019 Feb 7;9(2):561-570. doi: 10.1534/g3.118.200841.

A Noisy Analog-to-Digital Converter Connects Cytosolic Calcium Bursts to Transcription Factor Nuclear Localization Pulses in Yeast.

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Department of Cell & Systems Biology, University of Toronto, Toronto ON, Canada M5S 3B2.
Department of Cell & Systems Biology, University of Toronto, Toronto ON, Canada M5S 3B2


Several examples of transcription factors that show stochastic, unsynchronized pulses of nuclear localization have been described. Here we show that under constant calcium stress, nuclear localization pulses of the transcription factor Crz1 follow stochastic variations in cytosolic calcium concentration. We find that the size of the stochastic calcium bursts is positively correlated with the number of subsequent Crz1 pulses. Based on our observations, we propose a simple stochastic model of how the signaling pathway converts a constant external calcium concentration into a digital number of Crz1 pulses in the nucleus, due to the time delay from nuclear transport and the stochastic decoherence of individual Crz1 molecule dynamics. We find support for several additional predictions of the model and suggest that stochastic input to nuclear transport may produce noisy digital responses to analog signals in other signaling systems.


Crz1; calcineurin pathway; mathematical modelling; stochastic pulsing transcription factor; time delay model

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