Kin recognition and outer membrane exchange regulate social interactions in myxobacteria

摘要 生物学中一个基本的重要问题是多细胞内的单个细胞 有机体相互协作形成组织、器官和完整的有机体。一种解决办法是 这个复杂的问题是使用简单的模型系统，这些系统表现出在 组织中黄色粘球菌就是这样一个系统，例如， 数以千计的细胞聚集在一起，有节奏地移动，并建立子实体， 细胞分化成孢子。in m. xanthus我们发现了一个新的平台， 交互.这种行为涉及到亲属识别，其中细胞识别克隆体， 交换外膜（OM）蛋白质和脂质。外膜交换识别 (OME)是由一种叫做TraA的多态性细胞表面受体及其伴侣蛋白介导的 TraB.只有携带相同或非常相似的traA等位基因的细胞才会相互识别， OME。根据条件，OM含量的交换导致有益或有害的结果。 成果。在遗传模型中，我们发现OME可以导致受损的细胞的合作修复。 细胞在这里，健康的细胞补充突变细胞缺失的成分，恢复其功能。 健身在其他实例中，当多态性毒素被转移时，OME导致拮抗作用。 并且受体细胞不含同源免疫蛋白。虽然OME涉及 数百种不同的细胞成分的明显转移， 结果，该系统可用于可应用于细菌的强大方法。 research.这项建议涉及三个目标。在目标1中，我们将研究OM聚变， 通过使用显微镜，遗传和生物化学方法来确定交换机制， TraA和TraB的动态功能。目标2还将使用多种方法的组合来定义 TraA亲属识别的分子基础以及它如何与TraB相互作用。aim 3将进行调查 第二种途径允许OME递送的毒素进入细胞质。我们的初步 数据表明，这种亲属歧视系统影响了菌株多样化和种群 在自然土壤栖息地中发现的结构。这一假设将通过遗传学和 生物信息学实验最后，OME修复压力造成的损伤的能力 细胞将被测试。这些研究将有助于从分子水平上了解 亲属识别和OME，以及更深入地了解社会复杂的细菌 从个体转变为合作的多细胞组织。

Abstract A fundamentally important question in biology is how individual cells within multicellular organisms cooperate to form tissues, organs and a complete organism. One approach to address this complex question is to use simple model systems that exhibit many of the traits found in tissues. Myxococcus xanthus is one such system where, for instance, in response to starvation thousands of cells aggregate, move rhythmically and build fruiting bodies in which vegetative cells differentiate into spores. In M. xanthus we discovered a novel platform that mediates social interactions. This behavior involves kin recognition in which cells identify clonemates and exchange outer membranes (OM) proteins and lipids. Recognition in outer membrane exchange (OME) is mediated by a polymorphic cell surface receptor called TraA and its partner protein TraB. Only cells that bear identical or very similar alleles of traA will recognize one another for OME. Depending of conditions the exchange of OM content leads to beneficial or harmful outcomes. In genetic models we showed that OME can result in cooperative repair of damaged cells. Here, healthy cells replenish mutant cells with missing components that restores their fitness. In other examples, OME leads to antagonisms when polymorphic toxins are transferred and the recipient cells do not contain cognate immunity proteins. Although OME involves the apparent transfer of hundreds of different cellular components with complex social consequences, this system is amendable to powerful approaches that can be applied to bacterial research. This proposal addresses three goals. In Aim 1 we will investigate OM fusion as the mechanism for exchange by using microscopy, genetic and biochemical methods to define the dynamic functions of TraA and TraB. Aim 2 will also use a combination of approaches to define the molecular basis of TraA kin recognition and how it interacts with TraB. Aim 3 will investigate a second pathway that allows toxins delivered by OME to enter the cytoplasm. Our preliminary data suggests that this kin discrimination system impacts strain diversification and population structures found in natural soil habitats. This hypothesis will be tested by genetic and bioinformatic experiments. Last, the ability of OME to repair damage that is inflicted on stressed cells will be tested. These studies will lead to a molecular understanding of the mechanisms of kin recognition and OME, as well as a deeper insights into how a socially sophisticated bacterium transitions from individuals into a cooperative multicellular tissue.