Zinc Finger Protein Prz1 Regulates Ca2+ but Not Cl− Homeostasis in Fission Yeast

Abstract

10.1074/jbc.M212900200 Calcineurin is an important mediator that connects the Ca-dependent signaling to various cellular responses in a wide variety of cell types and organisms. In budding yeast, activated calcineurin exerts its function mainly by regulating the Crz1p/Tcn1 transcription factor. Here, we cloned the fission yeast gene, which encodes a zinc finger transcription factor highly homologous to Crz1/Tcn1. Similar to the results in budding yeast, calcineurin dephosphorylated Prz1 and resulted in the trans-location of Prz1 from the cytoplasm to the nucleus. Prz1 expression was stimulated by high extracellular Ca in a calcineurin-dependent fashion. However, unlike in budding yeast, the -null cells did not show any phenotype similar to those previously reported in calcineurin deletion such as aberrant cell morphology, mating defect, or hypersensitivity to Cl. Instead, the-null cells showed hypersensitivity to Ca, consistent with a dramatic decrease in transcription of Pmc1 Ca pump. Interestingly, overexpression of Prz1 did not suppress the Cl hypersensitivity of calcineurin deletion, and overexpression of Pmp1 MAPK phosphatase suppressed the Cl hypersensitivity of calcineurin deletion but not the Ca hypersensitivity of deletion. In addition, mutations in the , , and genes that showed synthetic lethal genetic interaction with calcineurin deletion did not exhibit synthetic lethality with the deletion. Our results suggest that calcineurin activates at least two distinct signaling branches, the Prz1-dependent transcriptional regulation and an unknown mechanism, which functions antagonistically with the Pmk1 MAPK pathway.