MILESTONES MILESTONE 21 The prokaryotic cytoskeleton Actin and tubulin are the major filaments in vitro, as was shown lack MreB, whereas those with complex components of the eukaryotic a little later. shapes, including rod and filamentous The first glimpse cytoskeleton. It was previously thought However, the most convincing forms, have one or more such genes. of filamentous that prokaryotes lacked a cytoskeleton. demonstration that FtsZ was the bacterial The helical bands observed by proteins inside However, research in the 1990s firmly counterpart of tubulin came when its Jones et al. were suggestive of a established that, in fact, the cytoskeleton crystal structure was solved by Löwe bacteria. Arguably cytoskeleton. van den Ent et al. provided originated in prokaryotes, with the and Amos. They revealed that FtsZ has direct evidence for this by showing that the beginning of discovery that filamentation temperature- an overall three-dimensional structure purified MreB forms polymers under ‘bacterial’ cell sensitive protein Z (FtsZ) is the bacterial that is similar to eukaryotic α-tubulin and various conditions in vitro. Electron biology. homologue of tubulin and MreB is the β-tubulin. FtsZ and tubulin also share microscopy showed that the polymers Jan Lowe homologue of actin. the way in which they initially assemble resembled one of the helical strands of FtsZ is a key player in bacterial into linear polymers with a longitudinal filamentous actin. They then determined cell division and acts at an early interface between two subunits that the crystal structure of MreB and found point in the pathway. The functional contains the GTPase active site. that it is remarkably similar to actin. These relationship between FtsZ and tubulin While the connection between FtsZ papers provided strong evidence that was uncertain because they share low and tubulin was being established, the MreB and actin are homologues. sequence identity at the amino-acid origin of actin remained obscure. In In the past decade, the discovery of level. FtsZ does, however, contain 2001, two papers by van den Ent et al. bacterial homologues of actin and tubulin a short tubulin signature sequence, and Jones et al. demonstrated that MreB revolutionized our view of bacterial cell which is known to be involved in the is the bacterial homologue of eukaryotic architecture. The coming period will binding of GTP to tubulin. The group actin. Based on sequence similarities, address important questions about the of Lutkenhaus initially showed FtsZ actin belongs to a large superfamily function and regulation of the bacterial to form a filamentous ring structure of proteins of unrelated function that cytoskeleton, and allow comparisons with during cell division and predicted it to includes the chaperone heat-shock the eukaryotic system. be a cytoskeletal element. Then, two protein-70 (Hsp70). Jones and colleagues Deepa Nath, Senior Editor, Nature independent groups led by Rothfield showed that MreB and the closely related and Park set out to test whether FtsZ protein Mbl are important for regulating ORIGINAL RESEARCH PAPERS Bi, E. & can also function as a GTP-binding the rod shape of Bacillus subtilis. Using Lutkenhaus, J. FtsZ ring structure associated with protein. Using biochemical assays, they light microscopy, they found that MreB division in Escherichia coli. Nature 354, 161 (1991) | RayChaudhuri, D. & Park, J. T. Escherichia coli cell- demonstrated that FtsZ purified from and Mbl form large spirals under the cell division gene ftsZ encodes a novel GTP-binding Cells that contain green bacterial cells can bind and hydrolyse membrane. Both proteins contribute protein. Nature 359, 251–254 (1992) | de Boer, P., fluorescent protein (GFP) GTP just like eukaryotic tubulin. to the determination of cell shape. Crossley, R. & Rothfield, L. The essential bacterial fusion to the MreB Furthermore, GTP binding was essential These proteins are conserved, with the cell-division protein FtsZ is a GTPase. Nature 359, paralogue Mbl in B. subtilis. 254–256 (1992) | Mukherjee, A., Dai, K. & Image courtesy of for the function of FtsZ in cell division existence of homologues in a wide range Lutkenhaus, J. Escherichia coli cell division R. Carballido-López and protein FtsZ is a guanine nucleotide binding J. Errington. University of of and also for its propensity to form of bacteria. In general, spherical bacteria protein. Proc. Natl Acad. Sci. USA 90, 1053–1057 Newcastle, UK. (1993) | Löwe, J. & Amos, L. A. Crystal structure of the bacterial cell-division protein FtsZ. Nature 391, 203–206 (1998) | Jones, L. J., Carballido- López, R. & Errington, J. Control of cell shape in bacteria: helical, actin-like filaments in Bacillus subtilis. Cell 104, 913–922 (2001) | van den Ent, F. & Löwe, J. Prokaryotic origin of the actin cytoskeleton. Nature 413, 39–44 (2001) FURTHER READING Ausmees, N., Kuhn, J.R. & Jacobs-Wagner, C. The bacterial cytoskeleton: an intermediate filament-like function in cell shape. Cell 115, 705–713 (2003) NATURE MILESTONES | CYTOSKELETON DECEMBER 2008.