TRANSDUCTION OF THE A SIGNAL IN MYXOCOCCUS DEVELOPMENT

粘球菌发育中 A 信号的转导

• 批准号: 6386301
• 负责人: HEIDI B KAPLAN
• 金额: $ 27.66万
• 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/6386301
• 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.

黄色粘球菌是一个很好的模型系统 细胞-细胞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的胚胎和成人有关。 传递信号以协调生长和生长等过程的细胞 分化，以及信令网络中有缺陷的细胞， 比如癌细胞。 通过早期多细胞发育的进展需要黄色微囊藻 细胞感知并对高密度和营养限制做出反应。二 敏感的传感网络监控这些细胞外信号，并在 黄花根结线虫发育早期的一个关键检查点。此检查点可以是 通过特定基因SPI的表达进行监测。这样做的长期目标是 研究将确定：i)细胞如何感知和转导 细胞密度信号？二)细胞密度和营养感知如何 路径整合？三)基因变化之间有什么联系 多细胞子实体的表达及其复杂行为反应 队形？ SPI的三个关键调控因子的鉴定和特性 Expression、SASS、SASR和SASN已经开始解决这些问题。vbl.使用 经典遗传学和分子遗传学与蛋白质生物化学相结合， 为这些蛋白质整合这两种蛋白质的机制产生了一个假说 细胞密度信号(细胞外A信号)和饥饿信号， 创造控制大脑发育过程中的表达的回路 反应性SPI基因。 为了验证这一假设，他们计划：i)分析依赖于SASS/SASR/SASN的 黄花莲早期细胞密度与饥饿信号的整合 开发，ii)生成体外转录系统以测试其活性 对SASS/SASR通路的研究，III)分析了对SASS/SASR通路的刺激 通过细胞表面完整性的改变，以及iv)调查 SASS/SASR非依赖性A类信号转导通路。他们的最终目标是 重建完整的信号通路，作为其功能的证据。