Yeast yapsins and cell wall assembly

酵母yapsin和细胞壁组装

• 批准号: 155285-2008
• 负责人: Bourbonnais, Yves
• 金额: $ 1.97万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=422509
• 关键词: Yeast; yapsins; cell; wall; assembly

Our laboratory is interested in the regulation and functional role of a unique family of fungal enzymes, collectively known as 'yapsins', in the assembly of the yeast cell wall. This structure is highly complex and essential for the viability of all fungi, including human opportunist pathogens such as C. albicans. The first member of this family is the Yps1 enzyme that we, and others, identified in the brewer yeast S. cerevisiae a decade ago. We now know that five members of theses enzymes are expressed in S. cerevisiae, all of them are localized at the cell surface. Recent studies suggested that these enzymes were implicated in some aspects of cell wall assembly, but until recently, no substrate for any of these enzymes had been identified. We recently identified some natural substrates for Yps1 in S. cerevisiae and the nature of these substrates clearly confirmed that Yps1 participate in the cell wall assembly. Our recent study also suggested that: 1) during their intracellular transport to reach the cell surface, these enzymes are kept apart from most other proteins destined for secretion; and 2) the environmental pH regulates the activity of this enzyme. In the current proposal we have designed experiments to: 1) identify additional Yps1 substrates; 2) confirm and understand the significance of the particular intracellular transport that this enzyme is taking; and 3) understand what controls the activity of this enzyme. In addition to deepen our understanding on how fungal yapsins regulate cell wall assembly in yeast, the proposed studies should help designing specific inhibitors that may lead to the development of novel antifungal agents.

我们的实验室对一种独特的真菌酶家族（统称为“yapsins”）在酵母细胞壁组装中的调节和功能作用感兴趣。这种结构非常复杂，对于所有真菌（包括白色念珠菌等人类机会病原体）的生存至关重要。这个家族的第一个成员是我们和其他人十年前在啤酒酵母中发现的 Yps1 酶。我们现在知道这些酶的五个成员在酿酒酵母中表达，它们都位于细胞表面。最近的研究表明，这些酶与细胞壁组装的某些方面有关，但直到最近，还没有鉴定出任何这些酶的底物。我们最近在酿酒酵母中鉴定了 Yps1 的一些天然底物，这些底物的性质清楚地证实了 Yps1 参与细胞壁组装。我们最近的研究还表明：1）在细胞内运输到达细胞表面的过程中，这些酶与大多数其他用于分泌的蛋白质保持分离； 2) 环境 pH 值调节该酶的活性。在当前的提案中，我们设计了实验来：1）识别额外的 Yps1 底物； 2) 确认并理解该酶所进行的特定细胞内转运的重要性； 3) 了解是什么控制着这种酶的活性。除了加深我们对真菌yapsins如何调节酵母细胞壁组装的理解之外，拟议的研究还应有助于设计可能导致新型抗真菌药物开发的特定抑制剂。