The Crz1/Sp1 transcription factor of Cryptococcus neoformans is activated by calcineurin and regulates cell wall integrity.
The Crz1/Sp1 transcription factor of Cryptococcus neoformans is activated by calcineurin and regulates cell wall integrity.
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DOI：
10.1371/journal.pone.0051403
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Djordjevic JT
中科院分区：
文献类型：
--
作者：
Lev S;Desmarini D;Chayakulkeeree M;Sorrell TC;Djordjevic JT
新型隐球菌能够在宿主温度下存活，并通过钙依赖性磷酸酶、钙调神经磷酸酶调节细胞壁的完整性。然而，新型隐球菌钙调神经磷酸酶的下游效应器在很大程度上是未知的。在酿酒酵母和其他真菌物种中，钙调神经磷酸酶依赖性转录因子 Crz1 在激活后易位到细胞核并触发靶基因的表达。我们现在表明，先前被确定为饥饿期间蛋白激酶 C 靶标的新型隐球菌 Crz1 直向同源物 (Crz1/Sp1)，在非饥饿条件下、细胞壁应激和高温生长期间是钙调神经磷酸酶的真正靶标。钙调神经磷酸酶缺陷突变体 Δcna1 和 CRZ1/SP1 突变体 (Δcrz1) 都对细胞壁干扰剂敏感。此外，两种突变体中几丁质合酶编码基因CHS6的表达均降低。我们追踪了在钙调神经磷酸酶抑制剂 FK506 存在和不存在的情况下，Crz1-GFP 在 WT C. neoformans 和 Δcna1 中对不同刺激的响应的亚细胞定位。暴露于高温（30-37°C 与 25°C）和细胞外钙会导致 Crz1-GFP 依赖钙调神经磷酸酶的核积累。出乎意料的是，1M 盐和热休克触发了不依赖钙调神经磷酸酶的 Crz1-GFP 在细胞质和核斑点内的隔离。据我们所知，与核靶向相反，点状胞质分布是新型隐球菌 Crz1 的独特特征。我们得出结论，根据环境条件，Crz1 会被钙/钙调神经磷酸酶依赖性和独立信号选择性激活。
Cryptococcus neoformans survives host temperature and regulates cell wall integrity via a calcium-dependent phosphatase, calcineurin. However, downstream effectors of C. neoformans calcineurin are largely unknown. In S. cerevisiae and other fungal species, a calcineurin-dependent transcription factor Crz1, translocates to nuclei upon activation and triggers expression of target genes. We now show that the C. neoformans Crz1 ortholog (Crz1/Sp1), previously identified as a protein kinase C target during starvation, is a bona fide target of calcineurin under non-starvation conditions, during cell wall stress and growth at high temperature. Both the calcineurin-defective mutant, Δcna1, and a CRZ1/SP1 mutant (Δcrz1) were susceptible to cell wall perturbing agents. Furthermore, expression of the chitin synthase encoding gene, CHS6, was reduced in both mutants. We tracked the subcellular localization of Crz1-GFP in WT C. neoformans and Δcna1 in response to different stimuli, in the presence and absence of the calcineurin inhibitor, FK506. Exposure to elevated temperature (30–37°C vs 25°C) and extracellular calcium caused calcineurin-dependent nuclear accumulation of Crz1-GFP. Unexpectedly, 1M salt and heat shock triggered calcineurin-independent Crz1-GFP sequestration within cytosolic and nuclear puncta. To our knowledge, punctate cytosolic distribution, as opposed to nuclear targeting, is a unique feature of C. neoformans Crz1. We conclude that Crz1 is selectively activated by calcium/calcineurin-dependent and independent signals depending on the environmental conditions.
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