Regulation of M. xanthus Social Gliding by Dif Pathway

黄色粘球菌在其发育生命周期中表现出最壮观的形态发生。为了应对饥饿，成千上万的细胞通过滑动运动聚集在一起，形成肉眼可见的多细胞子实体。成熟子实体内的营养细胞分化成休眠的、抗逆境的粘孢子。与任何已知的滑行细菌不同，黄色分枝杆菌具有两个滑行系统，即冒险(A)和社会(S)运动系统。A运动使黄花细胞能够作为孤立的个体运动，而S的运动则表现为大细胞群的运动。黄曲霉细胞如何相互作用和协调，从而产生S的运动，仍然是一个谜。一组新的基因，即dif基因，与S的运动有关。预测的dif基因产物与许多细菌的趋化蛋白具有很高的相似性。已知细菌趋化蛋白构成感官信号转导通路，负责细菌对环境刺激的策略性反应。Dif和趋化蛋白之间的相似性以及不同突变体的S运动缺陷强烈地表明，感觉成分参与了S运动的调节。这个项目采用了遗传学、分子生物学和生物化学的多学科方法来检验和巩固工作假说。将构建DIF突变，用于功能和结构研究。DIFA突变体的遗传抑制基因的特征是识别与DIF趋化信号转导途径具有功能、生化和/或物理相互作用的基因。在更广泛的背景下，该项目的成果有望促进我们对细胞-细胞相互作用和细胞间通信的理解，这些都是广泛存在的，并在各种生物系统和过程中发挥重要作用。

Myxococcus xanthus exhibits the most spectacular morphogenesis among bacteria during its developmental life cycle. In response to starvation, tens of thousands of cells move by gliding motility to aggregate and to form multicellular fruiting bodies visible to the naked eye. Vegetative cells within mature fruiting bodies differentiate into dormant and stress-resistant myxospores. Distinct from any other known gliding bacteria, M. xanthus possesses two gliding systems, the adventurous (A) and the social (S) motility systems. While A motility enables M. xanthus cells to move as isolated individuals, S motility is manifested as movement of large cell groups. It remains an enigma how M. xanthus cells interact and coordinate with one another to bring about S motility. A new set of genes, the dif genes, is implicated in S motility. The predicted dif gene products show high similarity to chemotaxis proteins from many bacteria. It is known that bacterial chemotaxis proteins constitute sensory signal transduction pathways that are responsible for bacterial tactic responses to environmental stimuli. The similarity between Dif and chemotaxis proteins and the S-motility defects of dif mutants strongly suggest the involvement of a sensory component in the regulation of S-motility. This project takes a multidisciplinary approach of genetics, molecular biology and biochemistry to examine and to consolidate working hypotheses. dif mutations will be constructed for functional and structural studies. Genetic suppressors of difA mutants will be characterized to identify genes with functional, biochemical and/or physical interactions with the dif chemotaxis-like signal transduction pathway. In a broader context, the outcome of this project is expected to advance our understanding of cell-cell interactions and intercellular communications, which are widespread and play essential roles in various biological systems and processes.