Myxococcus xanthus signaling and cell fate

黄色粘球菌信号传导和细胞命运

• 批准号: 8520340
• 负责人: Lawrence Joseph Shimkets
• 金额: $ 28.51万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8520340
• 关键词: Address; Adipose tissue; Adopted; Alcohol dehydrogenase; Antitoxins; Apoptosis; Bacteria; Biological; Biological Assay; Biological Models; Brain; Carbon; Cells; Chemoreceptors; Chemotactic Factors; Chemotaxis; Coupling; Cytolysis; Development; Equilibrium; Extracellular Matrix; Fatty Acids; Fruit; Gene Expression; Genes; Goals; Health; Homeostasis; Human; Individuality; Kidney; Life; Lipids; Liquid Chromatography; Mammals; Mass Fragmentography; Measures; Mediating; Metabolic; Metabolism; Methylation; Morphogenesis; Movement; Myxococcus; Myxococcus xanthus; Names; Obesity; Oxidoreductase; Pathway interactions; Phospholipids; Physiological; Physiology; Plasmalogens; Process; Prokaryotic Cells; Proteins; RNA Degradation; RNA Interference; Regulation; Regulon; Reproduction spores; Sensory; Signal Transduction; Structure; System; Testis; Tissues; Toxin; Triglycerides; Vesicle; Work; analog; branched chain fatty acid; cell type; chemical synthesis; innovation; intercellular communication; lipid metabolism; metabolic engineering; morphogens; mutant; novel; programs; protein-histidine kinase; public health relevance; receptor; relating to nervous system; response; transcription factor

DESCRIPTION (provided by applicant): Myxococcus xanthus has a unique developmental program with parallels in mammalian physiology and human health. The major metabolic products of early development are triglycerides that are stored in intracellular vesicles similar to those in mammalian adipose tissue. Cells inside the fruiting body have two principle fates. Programmed cell death (PCD), the fate of 80% of the cells, involves MazF toxin-mediated degradation of RNA. The remaining cells sporulate with the help of the MrpC antitoxin, a major developmental transcription factor. The decision to lyse or sporulate is mediated by three cell signals that also regulate synthesis of triglycerides. Lipid bodies in prespores are consumed for carbon and energy during spore maturation. Lipid bodies in cells undergoing PCD are released into the fruiting body where they regulate development. The proposal addresses two questions. First, what are the lipid morphogens? This work will identify the E-signal, the C-signal, and lipid chemoattractants in the first three specific aims through similar experimental approaches. The signals will be purified using bioassays involving mutants that are unable to produce the signals, identified by gas chromatography/mass spectrometry, then synthesized to prove that the synthetic structure has the activity. The second problem addressed by the proposal concerns the manner in which these signals determine cell fate. Specific aim 4 will examine the sensory pathway with a particular focus on the effect of each signal on the toxin/antitoxin interaction. When the toxin and antitoxin are balanced cells fail to choose a fate. We hypothesis that certain signals induce PCD by producing more free toxin while other signals stimulate sporulation by producing more antitoxin. This application is innovative because it will assemble up to four essential pieces in the puzzle of M. xanthus fruiting body morphogenesis and cell fate commitment. We expect to find that development flows in large measure out of the synthesis and utilization of lipid body lipids. Such lipids are an essential feature of mammalian development and homeostasis. This system may reveal novel regulatory strategies that are as yet undiscovered in mammals.

描述（由申请人提供）：