Zinc finger protein Prz1 regulates Ca2+ but not Cl- homeostasis in fission yeast -: Identification of distinct branches of calcineurin signaling pathway in fission yeast
Zinc finger protein Prz1 regulates Ca2+ but not Cl- homeostasis in fission yeast -: Identification of distinct branches of calcineurin signaling pathway in fission yeast
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DOI：
10.1074/jbc.m212900200
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发表时间：
2003-05-16
影响因子：
4.8
通讯作者：
Kuno, T
中科院分区：
文献类型：
--
作者：
Hirayama, S;Sugiura, R;Kuno, T
钙调神经磷酸酶是一种重要的介体，其将Ca 2+依赖性信号传导与多种细胞类型和生物体中的各种细胞反应联系起来。在芽殖酵母中，激活的钙调神经磷酸酶主要通过调节Crz 1 p/Tcn 1转录因子发挥其功能。在这里，我们克隆了裂殖酵母prz 1（+）基因，该基因编码与Crz 1/Tcn 1高度同源的锌指转录因子。与芽殖酵母中的结果类似，钙调磷酸酶使Prz 1去磷酸化，并导致Prz 1从细胞质易位到细胞核。Prz 1的表达被刺激高细胞外Ca 2+在钙调神经磷酸酶依赖的方式。然而，与芽殖酵母不同，prz 1-null细胞没有表现出任何与先前报道的钙调磷酸酶缺失类似的表型，如异常细胞形态，交配缺陷或对Cl-超敏反应。相反，prz 1-null细胞表现出对Ca 2+的超敏反应，这与Pmc 1 Ca 2+泵转录的急剧下降一致。有趣的是，Prz 1的过表达并不能抑制钙调磷酸酶缺失的Cl-超敏性，而Pmp 1 MAPK磷酸酶的过表达抑制钙调磷酸酶缺失的Cl-超敏性，但不能抑制prz 1缺失的Ca 2+超敏性。此外，在its 2（+）/cps 1（+）、its 8（+）和its 10（+）/cdc 7（+）基因中的突变显示出与钙调神经磷酸酶缺失的合成致死性遗传相互作用，而与prz 1缺失的突变没有显示出合成致死性。我们的研究结果表明，钙调磷酸酶激活至少两个不同的信号分支，即Prz 1依赖的转录调控和未知的机制，其功能与Pmk 1 MAPK通路拮抗。
Calcineurin is an important mediator that connects the Ca2+-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 prz1(+) 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 Ca2+ in a calcineurin-dependent fashion. However, unlike in budding yeast, the prz1-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 prz1-null cells showed hypersensitivity to Ca2+, consistent with a dramatic decrease in transcription of Pmc1 Ca2+ 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 Ca2+ hypersensitivity of prz1 deletion. In addition, mutations in the its2(+)/cps1(+), its8(+), and its10(+)/cdc7(+) genes that showed synthetic lethal genetic interaction with calcineurin deletion did not exhibit synthetic lethality with the prz1 deletion. Our results suggest that calcineurin activates at least two distinct signaling branches, i.e. the Prz1-dependent transcriptional regulation and an unknown mechanism, which functions antagonistically with the Pmk1 MAPK pathway.