Bacterial Cell Division: Minireview The Cycle of the Ring

Lawrence I. Rothfield and Sheryl S. Justice we may beclosing in on the prey. In a recent issue of Cell, Hale and de Boer (1997) described a newly identified Department of Microbiology University of Connecticut Health Center integral membrane protein, ZipA, that emerged from a direct search for genes coding for proteins that interact Farmington, Connecticut 06030 with FtsZ. ZipA has several properties expected of the FtsZ receptor and the evidence indicates that the ZipA– FtsZ interaction occurs at the midcell site at a very early The bacterial cell cycle can be arbitrarily divided into two segments: a DNA cycle that includes DNA replicastage of the division cycle. First, ZipA is an integral membrane protein that binds FtsZ in vitro. Second, ZipA tion and chromosome segregation, and a division cycle that leads to cytokinesis and cell separation. During the is required for cell division as shown by the formation of nonseptate filaments in the absence of ZipA. The division cycle, the cell must identify the midcell site at which division later occurs, differentiate this site in zipAnull filaments morphologically resemble ftsZnull filaments, rather than the filaments associated with loss preparation for cytokinesis, and finally form the division septum by the coordinate ingrowth of the cytoplasmic of other division genes that act at later stages of the division cycle. Third, in a growing population, a ZipA– membrane, the rigid murein (peptidoglycan) layer, and, in Gram-negative bacteria such as Escherichia coli, the green fluorescent protein (GFP) fusion protein is localized at midcell in essentially all cells. Finally, the distribuouter membrane of the cell envelope (Figure 1). Recent advances have led to an increased understanding of tion pattern of ZipA–GFP at the division site is similar to that of FtsZ, with ZipA being located in a ring that important elements of this complex series of events. Many, although probably not all, of the proteins inextends around the circumference of the cell. These observations indicate that ZipA is the FtsZ receptor or volved in the division cycle of E. coli are now known. One of these proteins, FtsZ, is now recognized to play interacts with FtsZ concurrently or soon after the initial FtsZ–membrane interaction. A choice between these a key role in the assembly of the division apparatus and in the process of cytokinesis. Its wide distribution and possibilities awaits the results of experiments to establish whether or not FtsZ can localize to the midcell site high degree of sequence conservation suggest that it probably plays a similar role in all bacterial and archaeal in the absence of ZipA. Stage II. Formation of the FtsZ Ring species. In this minireview, we discuss the likely sequence of events that occurs during differentiation of In a reaction that probably occurs shortly after its initial interaction with the membrane, the membrane-associthedivision apparatus of E. coli, beginningwith the localization of FtsZ at the potential division site and ending ated FtsZ forms an annular structure, the FtsZ ring, that is associated with the inner surface of the cytoplasmic with the generation of two new daughter cells (Figure 1). membrane and extends around the circumference of the cell (Lutkenhaus and Mukherjee, 1996). It is believed Stage I. FtsZ–Receptor Binding Studies by Lutkenhaus and his collaborators (Lutkenthat the FtsZ ring is produced by polymerization of FtsZ protomers. This is consistent with the observation that haus and Mukherjee, 1996) have established that FtsZ becomes localized at the future division site at an early FtsZ can be induced to polymerize in vitro, in a reaction that is facilitated by GTP, leading to the formation of stage in the division cycle and remains associated with the invaginating septum during cytokinesis. Because filamentous polymers whose protofilament structure is similar to that of microtubules (Erickson et al., 1996). FtsZ acts at an earlier stage of the division process than the other known components of the division machinery, There are 10,000–20,000 molecules of FtsZ per cell, enough to produce several continuous polymeric strucwith the possible exception of ZipA (see below), the interaction of FtsZ with the cytoplasmic membrane at tures around the waist of the cell. The ring may consist of one or more polymers that extend completely around the future division site is an obligatory early step in the sequence of events that culminates in septation and cell the cell, or it may be a series of shorter polymers organized to form a continuous annulus. FtsZ isolated from separation. The site-specific membrane recognition event implies the soluble fraction of the cell exists as an oligomer whose gel filtration behavior suggests a size of 10–15 the presence of a specific FtsZ receptor at midcell (Figure 1). Although the receptor has not yet been identified, monomers per oligomer. This is presumed to be the