Phosphoinositide signalling and fungal cell wall integrity: investigating the essential role of the conserved protein Ypp1

磷酸肌醇信号传导和真菌细胞壁完整性：研究保守蛋白 Ypp1 的重要作用

• 批准号: BB/E020550/1
• 负责人: Barry Panaretou
• 金额: $ 41.7万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE020550%2F1
• 关键词: Phosphoinositide; signalling; fungal; cell; wall

Living cells can tolerate extensive changes to their environment. Several signalling mechanisms exist which detect environmental changes, leading to activation of an appropriate response. We have identified Ypp1, a protein in baker's yeast, that is a key modulator of a particular signalling pathway contributing to maintenance of the fungal cell wall. Human cells don't have a cell wall, so this structure is regarded as a principal target for the development of antifungal agents which are non-toxic to humans. Signalling pathways in pathogenic fungi and baker's yeast are similar, so we will use baker's yeast as a model organism for investigating the role of Ypp1 in maintaining fungal cell wall integrity. The precise nature by which Ypp1 affects signalling will be determined, by measuring key biochemical intermediates of the signalling pathway involved. This will be followed by assessing how loss of Ypp1 affects the responses activated by the signalling pathway, with emphasis on how the chemical structure of the cell wall is re-modelled. Also, because the genome of baker's yeast can be manipulated with ease, we will identify pathways and proteins that involve the action of Ypp1. In this way, we will identify additional targets for antifungal drug design.

活细胞能忍受环境的巨大变化。存在几种信号机制，可以检测环境变化，从而激活适当的反应。我们已经确定了面包师酵母中的一种蛋白质Ypp1，它是一种特殊信号通路的关键调节剂，有助于维持真菌细胞壁。人类细胞没有细胞壁，因此这种结构被认为是开发对人类无毒的抗真菌药物的主要目标。病原真菌和面包酵母的信号通路相似，因此我们将以面包酵母为模型生物，研究Ypp1在维持真菌细胞壁完整性中的作用。通过测量所涉及的信号通路的关键生化中间体，将确定Ypp1影响信号传导的确切性质。接下来将评估Ypp1的缺失如何影响由信号通路激活的反应，重点是如何重新建模细胞壁的化学结构。此外，由于烘焙酵母的基因组可以很容易地操纵，我们将确定涉及Ypp1作用的途径和蛋白质。通过这种方式，我们将确定抗真菌药物设计的其他靶点。

项目成果

Ypp1/YGR198w plays an essential role in phosphoinositide signalling at the plasma membrane.

• DOI: 10.1042/bj20080209
• 发表时间: 2008-11
• 期刊: The Biochemical journal
• 作者: C. Zhai;Kuoyu Li;V. Markaki;J. Phelan;K. Bowers;F. Cooke;B. Panaretou