Self-nonself recognition and multicellularity in myxobacteria

摘要 生物学中的一个基本问题是多细胞有机体中的单个细胞如何 将其他细胞识别为自我，以便在组织、器官和整个个体中协同运作。 为了解决这个复杂的问题，我们研究了一个相对简单和可实验跟踪的 模式生物，黄色粘球菌。虽然黄色分枝杆菌是一种细菌，但它表现出许多特征 发现于组织和更复杂的多细胞物种中。其中一个特征是多细胞发育 对饥饿的反应。我们发现，细胞的另一个特征是区分 用于细胞蛋白质和脂类交换的自体和非自体。识别是由一个 多态的细胞表面受体称为TRAA及其伙伴TRAB。只有携带相同基因的细胞 或者几乎相同的TraA受体通过同型相互作用进行。由此产生的社会后果 过程，称为外膜交换(OME)，根据不同的性质而有所不同 相互作用的细胞。在某些情况下，OME导致了合作互动，健康的捐赠者 通过补充受损细胞的成分来修复受损细胞。在其他情况下，OME会导致 当配对细胞不是克隆细胞时的拮抗作用。由多态毒素引起的歧视 转移到缺乏同源免疫的受体细胞。 我们未来的目标是多方面的，包括对OME的理解，以及更广泛地说，如何 细胞识别自我，并向多细胞转变。在接下来的五年里，我们将关键地 研究OME如何带来协作性。调查的一个领域是TraA/B如何指导 群体中的紧急行为，包括同步和协调的运动。这 将通过监测全球基因表达以及TraA/B如何与信号相互作用来探索 控制运动的转导途径。细胞同步正在用生物传感器进行研究 监测器监测细胞内的钙离子流量。其他方法将探索黄曲霉是如何回应和 适应环境压力，从而将这些适应转移到幼稚的人群中 由OME提供。第二个研究领域是粘性细菌如何迅速分化成不同的 自然环境中的社会群体。我们的初步发现表明，水平基因 非裂解转导粒子的转移通过携带多态基因介导种群分化 涉及社会歧视的基因。第三个焦点领域将阐明OME的机制 被认为涉及外膜融合。最后，我们将探索新的自我机制 识别及其在多细胞生命中的作用。

Abstract A fundamental question in biology is how individual cells within a multicellular organism recognize other cells as self to cooperatively function in tissues, organs and as whole individuals. To address this complex question, we study a relatively simple and experimentally trackable model organism, Myxococcus xanthus. Although a bacterium, M. xanthus exhibits many traits found in tissues and more complex multicellular species. One trait is multicellular development in response to starvation. Another trait, we discovered, is the ability of cells to distinguish between self and nonself for the exchange of cellular proteins and lipids. Recognition is mediated by a polymorphic cell surface receptor called TraA and its partner TraB. Only cells that bear identical or nearly identical TraA receptors engage by homotypic interactions. Social outcomes from this process, called outer membrane exchange (OME), vary depending on the properties of the interacting cells. In some cases, OME leads to cooperative interactions whereby healthy donors repair damaged cells by replenishing their cell components. In other cases, OME leads to antagonism when partnering cells are not clonal. Discrimination occurs by polymorphic toxin transfer to recipient cells that lack cognate immunity. Our future goals are multifaceted with respect to understanding OME and, more broadly, how cells recognize self and transition toward multicellularity. Over the next five years we will critically examine how OME leads to cooperativity. One area of investigation is how TraA/B directs emergent behaviors in populations that include synchronized and coordinated movements. This will be explored by monitoring global gene expression and how TraA/B interacts with a signal transduction pathway that controls motility. Cell synchronization is being studied with a biosensor the monitors’ calcium fluxes in cells. Other approaches will probe how M. xanthus responds and adapts to environmental stresses, whereby those adaptations are transferred to naïve populations by OME. A second area of research addresses how myxobacteria rapidly diverge into different social groups in natural environments. Our preliminary findings indicate that horizontal gene transfer by non-lytic transducing particles mediate population divergence by carrying polymorphic genes involved in social discrimination. A third focus area will elucidate the mechanism of OME thought to involve outer membrane fusion. Finally, we will explore new mechanisms of self- recognition and its role in multicellular life.