Signaling iteractions in cytokinesis, cell wall biogenesis, and growth in fungi

真菌胞质分裂、细胞壁生物发生和生长中的信号交互

• 批准号: 8132355
• 负责人: JOSE R RODRIGUEZ-MEDINA
• 金额: $ 25.73万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8132355
• 关键词: Actomyosin; Affect; Antifungal Agents; Biochemical; Biogenesis; Biological Process; Cell Survival; Cell Wall; Cell membrane; Cells; Cellular Stress; Characteristics; Complement; Complex; Cytokinesis; Data; Defect; Development; Down-Regulation; Exhibits; Gene Expression; Genes; Genetic; Genetic Transcription; Goals; Growth; Interruption; Knowledge; Lead; Link; Messenger RNA; Metabolism; Mutation; Myosin ATPase; Myosin Type II; Overlapping Genes; Pathway interactions; Phenotype; Process; Proteins; Ribosomal Proteins; Saccharomyces cerevisiae; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Stress; Testing; Transcriptional Activation; Transducers; Translational Regulation; Yeasts; biological adaptation to stress; cell growth; fungus; gene repression; mRNA Expression; mutant; research study; response; sensor

DESCRIPTION (provided by applicant): The scientific goals of this application are to 1- understand signaling interactions connecting myosin II functions in cytokinesis, cell wall biogenesis, and cell growth 2- understand the relation between myosin II function and cell wall integrity and 3- identify new potential targets for antifungal drugs. We will accomplish this by identifying what metabolic processes are affected by the interruption of cytokinesis by actomyosindependent and actomyosin-independent mutations, what signaling pathways are necessary for cell survival under these conditions, and the biochemical components linking these pathways in these genetic mutants. Myosin ll-deficient Saccharomyces cerevisiae cells (myolA) exhibit multiple phenotypes with characteristics of both cytokinesis and cell wall mutants. To determine if these phenotypes were related to changes in gene expression, we determined the global transcription profile of myol A strains. These studies corroborated that the PKC1-dependent signaling pathway coordinately activates the transcription of cell wall stress genes in these strains. Coordinated down-regulation of ribosomal protein genes also occurs and it was observed that over expression of ribosomal protein genes RPL30 and RPS31 partially restored cell wall function in a myol A strain. Our main hypothesis is that transcriptional activation of cell wall stress genes and the down-regulation of ribosomal protein genes in myol A strains represent separate phenotypes for cell wall and cytokinesis mutants, respectively; each employing distinct essential signaling pathways that are interconnected. To test this hypothesis our specific aims are to: 1- conduct mRNA transcription analysis of the cytokinesis mutant chs2A and the cell wall mutant fksl A for subsequent comparison with myolA strains, 2-conduct analysis of mRNA translational regulation in cytokinesis mutants, 3- determine the status of the PKC1, TOR1, and TOR2 signaling pathways in cytokinesis mutant strains and test their requirement for cell viability, and 4- identify common regulators of the PKC1 and TOR signaling pathways in cytokinesis and cell wall mutants. The significance of this study lies in the discovery of new regulatory connections that coordinate actomyosin function and cell wall biogenesis in fungal cells. The proposed study will also increase our understanding about how loss of myosin II contributes to the stress response in yeast cells. Knowledge of the interaction between myosin II and stress signaling can lead to identification of potential targets for new antifungal drugs.

描述（由申请人提供）：本应用的科学目标是1-了解连接肌球蛋白II功能，细胞壁生物发生和细胞生长的信号传导相互作用2-了解肌球蛋白II功能与细胞壁完整性与3-确定抗真菌药物的新潜在目标之间的关系。我们将通过确定哪些代谢过程会受到肌动肌依赖性和肌动蛋白独立的突变的细胞因子的中断影响，在这些条件下细胞存活以及这些遗传突变体中这些途径连接这些途径的生物化学成分所必需的信号传导途径。肌球蛋白LL缺陷型酿酒酵母细胞（Myola）表现出多种表型，具有细胞因子和细胞壁突变体的特征。为了确定这些表型是否与基因表达的变化有关，我们确定了Myol A菌株的全局转录曲线。这些研究证实了PKC1依赖性信号通路协同激活这些菌株中细胞壁应力基因的转录。还会发生核糖体蛋白基因的协调下调，并且观察到核糖体蛋白基因的表达RPL30和RPS31在Myol A菌株中部分恢复了细胞壁功能。我们的主要假设是，细胞壁应激基因的转录激活和米尔A菌株中核糖体蛋白基因的下调分别代表细胞壁和细胞因子突变体的单独表型。每种采用互连的不同基本信号通路。为了检验该假设，我们的具体目的是：1-对细胞因子突变体CHS2A和细胞壁突变体FKSL A进行mRNA转录分析，以便与Myola菌株进行比较，对细胞因子突变体中mRNA翻译调节的2导能分析，3-确定pKC1和Torak for tor 2，cy tor 2 cy int tor 2 cy tor 2 cy int cytok int tor 2 cy tor 2 cy int tor 2 cytok int tor 2 cy int cytok int tor 2 cy tor 2 cy int tor 2 cy tor 2 cy tor 2 cy tor 2 cy int cytok。生存能力和4-鉴定PKC1和TOR信号通路的常见调节剂中的细胞因子和细胞壁突变体中。这项研究的意义在于发现了新的调节连接，这些调节连接是在真菌细胞中协调肌动蛋白功能和细胞壁生物发生的。拟议的研究还将提高我们对肌球蛋白II损失如何促进酵母细胞的压力反应的理解。了解肌球蛋白II与压力信号传导之间的相互作用可以导致鉴定新的抗真菌药物的潜在靶标。