Phosphorylation of Rga2, a Cdc42 GAP, by CDK/Hgc1 is crucial for Candida albicans hyphal growth
Phosphorylation of Rga2, a Cdc42 GAP, by CDK/Hgc1 is crucial for Candida albicans hyphal growth
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DOI：
10.1038/sj.emboj.7601814
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发表时间：
2007-08-22
期刊：
影响因子：
11.4
通讯作者：
Wang, Yue
中科院分区：
文献类型：
--
作者：
Zheng, Xin-De;Lee, Raymond Teck Ho;Wang, Yue
细胞周期蛋白依赖性激酶（CDKs）控制酵母形态发生，尽管它们如何调节极性机制仍不清楚。二型真菌白色念珠菌使用Cdc 28/Hgcl，CDK/细胞周期蛋白复合物，以促进持续的肌动蛋白极化菌丝生长。在这里，我们报告，Rga 2，一个GT3激活蛋白（GAP）的中央极性调节Cdc 42，经历汞依赖性过度磷酸化。利用类似物敏感的Cdc 28作为突变体，我们证实Cdc 28在体外和体内控制Rga 2磷酸化。删除RGA 2产生细长的酵母细胞，菌丝形态发生没有明显的影响。然而，删除它或失活其GAP活性恢复三角洲hgc 1突变体的菌丝生长，这表明Rga 2抑制菌丝发育和Cdc 28/Hgc 1灭活它在菌丝诱导。我们提供的证据表明，Cdc 28/Hgc 1可能会采取行动，以防止Rga 2本地化的菌丝尖端，导致本地化Cdc 42激活菌丝延伸。Rga 2在芽出现时也经历了短暂的Cdc 28依赖性过度磷酸化，这表明通过CDKs调节Cdc 42的GAP可能在酵母中不同形式的极化形态发生中发挥重要作用。这项研究揭示了CDKs和极性机制之间的直接分子联系。
Cyclin-dependent kinases (CDKs) control yeast morphogenesis, although how they regulate the polarity machinery remains unclear. The dimorphic fungus Candida albicans uses Cdc28/Hgcl, a CDK/cyclin complex, to promote persistent actin polarization for hyphal growth. Here, we report that Rga2, a GTPase- activating protein (GAP) of the central polarity regulator Cdc42, undergoes Hgcl-dependent hyperphosphorylation. Using the analogsensitive Cdc28as mutant, we confirmed that Cdc28 controls Rga2 phosphorylation in vitro and in vivo. Deleting RGA2 produced elongated yeast cells without apparent effect on hyphal morphogenesis. However, deleting it or inactivating its GAP activity restored hyphal growth in Delta hgc1 mutants, suggesting that Rga2 represses hyphal development and Cdc28/Hgc1 inactivates it upon hyphal induction. We provide evidence that Cdc28/Hgc1 may act to prevent Rga2 from localizing to hyphal tips, leading to localized Cdc42 activation for hyphal extension. Rga2 also undergoes transient Cdc28- dependent hyperphosphorylation at bud emergence, suggesting that regulating a GAP(s) of Cdc42 by CDKs may play an important role in governing different forms of polarized morphogenesis in yeast. This study reveals a direct molecular link between CDKs and the polarity machinery.