Spatiotemporal dynamics of the calcineurin target CrzA.

The response of Aspergilli to elevated concentrations of extracellular calcium and manganese, or environmental alkalinization is mediated by CrzA, a calcineurin-responsive transcription factor (TF). CrzA is the effector of a signaling pathway which includes the apical protein's calmodulin and calcineurin, and the protein kinases GskA and CkiA. Preferentially located in the cytoplasm, CrzA is the only element of the pathway modifying its localization under those stress conditions, being imported into nuclei. Remarkably, there is a direct relationship between the nature/intensity of the stimulus and the pace of nuclear import and time of nuclear permanence of CrzA. Alkalinity caused a transient nuclear accumulation of CrzA while high Ca and Mn concentrations generated a long-lasting accumulation. Furthermore, Ca concentrations (below 5mM) that are non-toxic for a crzAΔ mutant promoted full signaling of CrzA. However, micromolar concentrations or a mutation disrupting the interaction of CrzA with the phosphatase complex calcineurin, permitted the visualization of a transient and polarized nuclear accumulation of the TF in a tip-to-base gradient. Overall, these results support a model in which nucleo-cytoplasmic dynamics and transcriptional activity of CrzA are driven by apical signals transmitted by calmodulin and calcineurin. This communication is essential to understand Ca-induced stress response in fungi.