TRANSDUCTION OF THE A SIGNAL IN MYXOCOCCUS DEVELOPMENT

粘球菌发育中 A 信号的转导

• 批准号: 6519491
• 负责人: HEIDI B KAPLAN
• 金额: $ 27.6万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6519491
• 关键词: Myxococcus; bacterial genetics; biological signal transduction; cell cell interaction; cell type; chimeric proteins; developmental genetics; gene expression; gene mutation; genetic regulatory element; lipopolysaccharides; microorganism growth; regulatory gene; subtraction hybridization; transcription factor

Myxococcus xanthus represents an excellent model system to address fundamental questions of how cell-cell signaling pathways control multicellular development. These questions are relevant to all normal embryonic and adult cells that transduce signals to coordinate processes such as growth and differentiation, as well as to cells that are defective in signaling networks, such as cancer cells. Progression through early multicellular development requires that M. xanthus cells sense and respond to a high cell density and nutrient limitation. Two sensitive sensing networks monitor these extracellular signals and converge at a critical checkpoint early in M. xanthus development. This check -point can be monitored by expression of a specific gene, spi. The long-term goals of this research are to determine: i) How do the cells sense and transduce the cell-density signal? ii) How are the cell-density- and nutrient-sensing pathways integrated? iii) What is the connection between the change in gene expression and the complex behavioral response of multicellular fruiting body formation? The identification and characterization of three critical regulators of spi expression, SasS, SasR, and SasN has begun to address these questions. Using classical and molecular genetics combined with protein biochemistry, they have generated a hypothesis for the mechanism by which these proteins integrate both the cell-density signal (extracellular A signal) and the starvation signal, creating the circuitry that controls the developmental expression of the responsive spi gene. To test this hypothesis, they plan to: i) analyze the SasS/SasR/SasN-dependent integration of cell density and starvation signals during early M. xanthus development, ii) generate an in vitro transcription system to test the activity of the SasS/SasR pathway, iii) analyze the stimulation of the SasS/SasR pathway by alterations in cell-surface integrity, and iv) investigate SasS/SasR-independent A signal transduction pathways. Their ultimate goal is to reconstitute the complete signaling pathway as proof of its function.

黄色粘球菌代表了一个优秀的模型系统来解决 细胞间信号通路如何控制多细胞的基本问题 发展。这些问题与所有正常胚胎和成人有关 转导信号以协调生长等过程的细胞 分化，以及信号网络有缺陷的细胞， 例如癌细胞。 早期多细胞发育的进展需要 M. xanthus 细胞感知并响应高细胞密度和营养限制。二 敏感的传感网络监测这些细胞外信号并汇聚在 M. xanthus 发育早期的一个关键检查点。这个检查点可以是 通过特定基因 spi 的表达进行监测。本次活动的长期目标 研究的目的是确定： i) 细胞如何感知和转导 细胞密度信号？ ii) 细胞密度和营养感应如何 整合途径？ iii) 基因变化之间有什么联系 多细胞子实体的表达和复杂的行为反应 形成？ SPI 三个关键调节因子的识别和表征 expression、SasS、SasR 和 SasN 已经开始解决这些问题。使用 经典和分子遗传学与蛋白质生物化学相结合，他们有 对这些蛋白质整合两者的机制提出了假设 细胞密度信号（细胞外 A 信号）和饥饿信号， 创建控制发育表达的电路 反应性spi基因。 为了检验这一假设，他们计划： i) 分析 SasS/SasR/SasN 依赖性 早期 M. xanthus 期间细胞密度和饥饿信号的整合 开发，ii) 生成体外转录系统来测试活性 SasS/SasR 通路的分析，iii) 分析 SasS/SasR 通路的刺激 通过改变细胞表面完整性，以及 iv) 研究 SasS/SasR 独立 A 信号转导途径。他们的最终目标是 重建完整的信号通路作为其功能的证明。