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: 7498093
• 负责人: JOSE R RODRIGUEZ-MEDINA
• 金额: $ 26.25万
• 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 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7498093
• 关键词: Actomyosin; Affect; Antifungal Agents; Biochemical; Biogenesis; Biological Process; Cell Survival; Cell Wall; Cell membrane; Cells; Characteristics; Complement; Complex; Condition; Cytokinesis; Data; Defect; Depth; 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）：本申请的科学目标是 1- 了解连接胞质分裂、细胞壁生物发生和细胞生长中肌球蛋白 II 功能的信号相互作用 2- 了解肌球蛋白 II 功能与细胞壁完整性之间的关系 3- 确定抗真菌药物的新潜在靶点。我们将通过确定哪些代谢过程受到肌动球蛋白依赖性和肌动球蛋白非依赖性突变导致的胞质分裂的影响，在这些条件下细胞生存需要哪些信号传导途径，以及在这些基因突变体中连接这些途径的生化成分来实现这一目标。肌球蛋白 II 缺陷的酿酒酵母细胞 (myolA) 表现出多种表型，具有胞质分裂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 菌株的整体转录谱。这些研究证实，PKC1 依赖性信号通路协调激活这些菌株中细胞壁应激基因的转录。核糖体蛋白基因的协调下调也发生，并且观察到核糖体蛋白基因RPL30和RPS31的过度表达部分恢复了myol A菌株的细胞壁功能。我们的主要假设是，myol A 菌株中细胞壁应激基因的转录激活和核糖体蛋白基因的下调分别代表细胞壁和胞质分裂突变体的不同表型；每一种都采用相互关联的独特的重要信号传导途径。为了检验这一假设，我们的具体目标是：1-对胞质分裂突变体 chs2A 和细胞壁突变体 fksl A 进行 mRNA 转录分析，以便随后与 myolA 菌株进行比较，2-对胞质分裂突变体中的 mRNA 翻译调控进行分析，3-确定胞质分裂突变体菌株中 PKC1、TOR1 和 TOR2 信号通路的状态并测试其对细胞的需求 活力，4- 识别胞质分裂和细胞壁突变体中 PKC1 和 TOR 信号通路的常见调节因子。这项研究的意义在于发现了协调真菌细胞中肌动球蛋白功能和细胞壁生物发生的新调控连接。这项研究还将加深我们对肌球蛋白 II 的缺失如何影响酵母细胞应激反应的理解。了解肌球蛋白 II 和应激信号传导之间的相互作用可以帮助识别新抗真菌药物的潜在靶点。