Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
Biozentrum, University of Basel, Basel, Switzerland
mBio. 2020 Apr 28;11(2):e00487-20. doi: 10.1128/mBio.00487-20.
Cell division requires proper spatial coordination with the chromosome, which undergoes dynamic changes during chromosome replication and segregation. FtsZ is a bacterial cytoskeletal protein that assembles into the Z-ring, providing a platform to build the cell division apparatus. In the model bacterium , the cellular localization of the Z-ring is controlled during the cell cycle in a chromosome replication-coupled manner. Although dynamic localization of the Z-ring at midcell is driven primarily by the replication origin-associated FtsZ inhibitor MipZ, the mechanism ensuring accurate positioning of the Z-ring remains unclear. In this study, we showed that the Z-ring colocalizes with the replication terminus region, located opposite the origin, throughout most of the cell cycle. Spatial organization of the two is mediated by ZapT, a previously uncharacterized protein that interacts with the terminus region and associates with ZapA and ZauP, both of which are part of the incipient division apparatus. While the Z-ring and the terminus region coincided with the presence of ZapT, colocalization of the two was perturbed in cells lacking , which is accompanied by delayed midcellular positioning of the Z-ring. Moreover, cells overexpressing ZapT showed compromised positioning of the Z-ring and MipZ. These findings underscore the important role of ZapT in controlling cell division processes. We propose that ZapT acts as a molecular bridge that physically links the terminus region to the Z-ring, thereby ensuring accurate site selection for the Z-ring. Because ZapT is conserved in proteobacteria, these findings may define a general mechanism coordinating cell division with chromosome organization. Growing bacteria require careful tuning of cell division processes with dynamic organization of replicating chromosomes. In enteric bacteria, ZapA associates with the cytoskeletal Z-ring and establishes a physical linkage to the chromosomal replication terminus through its interaction with ZapB-MatP-DNA complexes. However, because ZapB and MatP are found only in enteric bacteria, it remains unclear how the Z-ring and the terminus are coordinated in the vast majority of bacteria. Here, we provide evidence that a novel conserved protein, termed ZapT, mediates colocalization of the Z-ring with the terminus in , a model organism that is phylogenetically distant from enteric bacteria. Given that ZapT facilitates cell division processes in , this study highlights the universal importance of the physical linkage between the Z-ring and the terminus in maintaining cell integrity.
细胞分裂需要与染色体进行适当的空间协调，而染色体在复制和分离过程中会发生动态变化。FtsZ 是一种细菌细胞骨架蛋白，它组装成 Z 环，为构建细胞分裂装置提供了一个平台。在模式细菌中，Z 环的细胞定位在细胞周期中通过与染色体复制偶联的方式进行控制。虽然 Z 环在细胞中部的动态定位主要由与复制起点相关的 FtsZ 抑制剂 MipZ 驱动，但确保 Z 环准确定位的机制仍不清楚。在这项研究中，我们表明 Z 环与位于复制起点对面的复制末端区域在细胞周期的大部分时间都共定位。这两个区域的空间组织是由 ZapT 介导的，ZapT 是一种以前未被表征的蛋白，它与末端区域相互作用，并与 ZapA 和 ZauP 结合，ZapA 和 ZauP 都是起始分裂装置的一部分。当 Z 环和末端区域存在 ZapT 时，两者发生共定位，但在缺失 的细胞中，两者的共定位受到干扰，同时 Z 环在细胞中部的定位也会延迟。此外，过表达 ZapT 的细胞中 Z 环的定位受损，MipZ 也受到干扰。这些发现强调了 ZapT 在控制细胞分裂过程中的重要作用。我们提出，ZapT 充当分子桥，将末端区域与 Z 环物理连接起来，从而确保 Z 环的准确定位。由于 ZapT 在变形菌中是保守的，这些发现可能定义了一种协调细胞分裂与染色体组织的一般机制。生长中的细菌需要通过动态组织复制染色体来仔细调整细胞分裂过程。在肠细菌中，ZapA 与细胞骨架 Z 环结合，并通过与 ZapB-MatP-DNA 复合物的相互作用与染色体复制末端建立物理连接。然而，由于 ZapB 和 MatP 只存在于肠细菌中，因此仍然不清楚 Z 环和末端在绝大多数细菌中是如何协调的。在这里，我们提供的证据表明，一种新的保守蛋白，称为 ZapT，介导了 在 中 Z 环与末端的共定位， 是一种与肠细菌在系统发育上相距甚远的模式生物。鉴于 ZapT 促进 在细胞分裂过程中的作用，这项研究强调了 Z 环和末端之间物理连接在维持细胞完整性方面的普遍重要性。
