Bursting into the nucleus

Abstract

An increase in extracellular Ca(2+) induces the nuclear localization of the Crz1 transcription factor and the activation of target genes in yeast. A recent study indicates that nuclear entry occurs in short stochastic bursts that are unsynchronized within the population of cells. The frequency but not the amplitude of the bursts is controlled by Ca(2+). Modulation of the frequency of the burst coordinates aspects of expression of Crz target genes.

Fig. 1

(A) Crz1 enters the nucleus in short stochastic bursts lasting about 2 min after undergoing dephosphorylation in the cytoplasm by the calcium-activated phosphatase calcineurin (Cn) (1, 19). The mechanism through which Crz1 exits the nucleus is not clear. (B) NFATc proteins are similar to Crz1 in that they are dephosphorylated by calcineurin on similar motifs and enter the nucleus, where they combine with other proteins to form complexes on the regulatory regions of target genes (16). The SRR is the serine-rich region, which is multiply phosphorylated. (C) Feedback loops in the calcineurin/NFAT signaling pathway predict oscillation with certain parameters (such as concentrations of the proteins) of the pathway that might be achieved in specific tissues. k, reaction constant. Occ refers to occluded or inactive state for calcineurin. (D) NFAT target genes are activated in a stochastic manner with the probability of being in the on state determined by time after stimulation with Ca²⁺ (9).

Fig. 2

FM coordination. A field of cells undergoing brief stochastic bursts of Ca²⁺ entry (A) are brought to coordinated behavior with proportional target gene expression. Gray nuclei in (A) represent bursts of Crz1 nuclear localization; green nuclei are those in which Crz1 bursts are not taking place. (B) Both promoters show similar responses to Ca²⁺ concentration.