cAMP-dependent protein kinase involves calcium tolerance through the regulation of Prz1 in Schizosaccharomyces pombe

The cAMP-dependent protein kinase Pka1 is known as a regulator of glycogenesis, meiosis, and stress responses in Schizosaccharomyces pombe. We demonstrated that Pka1 is responsible for calcium tolerance. Loss of functional components of the PKA pathway such as Git3, Gpa2, Cyr1, and Pka1 yields a CaCl2-sensitive phenotype, while loss of Cgs1, a regulatory subunit of PKA, results in CaCl2 tolerance. Cytoplasmic distribution of Cgs1 and Pka1 is increased by the addition of CaCl2, suggesting that CaCl2 induces dissociation of Cgs1 and Pka1. The expression of Prz1, a transcriptional regulator in calcium homeostasis, is elevated in a pka1∆ strain and in a wild type strain under glucose-limited conditions. Accordingly, higher expression of Prz1 in the wild type strain results in a CaCl2-sensitive phenotype. These findings suggest that Pka1 is essential for tolerance to exogenous CaCl2, probably because the expression level of Prz1 needs to be properly regulated by Pka1.cAMP依赖性蛋白激酶Pka1（cAMP-dependent protein kinase Pka1）在粟酒裂殖酵母（Schizosaccharomyces pombe）中被认为是糖原生成、减数分裂及应激反应的调控因子。本研究证实，Pka1同样参与钙离子耐受的调控。PKA通路的功能缺失组分（如Git3、Gpa2、Cyr1及Pka1）会使菌株呈现氯化钙敏感表型；而PKA的调节亚基Cgs1的缺失，则会使菌株获得氯化钙耐受表型。添加氯化钙可提升Cgs1与Pka1的细胞质分布水平，提示氯化钙可诱导二者发生解离。在pka1Δ缺失菌株以及葡萄糖限制条件下的野生型菌株中，钙稳态转录调控因子Prz1的表达水平均会上调。相应地，野生型菌株中Prz1的高表达会导致氯化钙敏感表型。上述研究结果表明，Pka1对外源性氯化钙的耐受至关重要，这可能是因为Prz1的表达水平需要由Pka1进行精准调控。