Kin recognition and outer membrane exchange regulate social interactions in myxobacteria

摘要 生物学中一个根本性的重要问题是多细胞中的单个细胞如何 生物体相互协作，形成组织、器官和一个完整的有机体。一种解决问题的方法 这个复杂的问题是使用简单的模型系统，这些系统展示了 纸巾。例如，黄色粘球菌就是这样一种系统，在这种系统中，为了应对饥饿 数以千计的细胞聚集在一起，有节奏地移动，并建立子实体，在其中营养 细胞分化为孢子。在M.xansights中，我们发现了一个新的平台，它调解了社会 互动。这种行为涉及亲缘关系识别，即细胞识别克隆和 交换外膜(OM)蛋白质和脂质。外膜交换中的识别 (OME)是由一种称为TraA的多态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等位基因的细胞才能相互识别 好的。根据条件的不同，OM内容的交换会导致有益或有害 结果。在遗传模型中，我们证明了OME可以导致损伤的合作修复 细胞。在这里，健康细胞用缺失的成分补充突变细胞，这些成分可以恢复它们的 健身。在其他例子中，当多态毒素被转移时，OME会导致拮抗 受体细胞不含同源免疫蛋白。尽管OME涉及 数百个不同的蜂窝组件与复杂的社交网络的明显转移 结果，这个系统可以修改为强大的方法，可以应用于细菌 研究。这项提案涉及三个目标。在目标1中，我们将研究OM融合作为 通过使用显微镜、遗传学和生化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-kin识别的分子基础及其与TRAb的相互作用。AIM 3将调查 第二条途径，允许OME传递的毒素进入细胞质。我们的预赛 数据表明，这种亲属歧视制度影响了品系多样性和种群数量。 在自然土壤栖息地中发现的结构。这一假说将通过基因和 生物信息学实验。最后，OME修复压力造成的损害的能力 细胞将接受测试。这些研究将使人们从分子水平上了解其发病机制 亲缘关系识别和OME，以及对一种社会复杂的细菌如何 从个体过渡到合作的多细胞组织。

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.