Tubulin is a major component of the eukaryotic cytoskeleton, controlling cell shape, structure and dynamics, whereas its bacterial homolog FtsZ establishes the cytokinetic ring that constricts during cell division. Although these proteins share a GTP-dependent ability to oligomerise into filaments, how such different biological roles of tubulin and FtsZ evolved is unknown. Our interest in this question led to the archaea, which have a prokaryotic cell layout, but are phylogenetically more related to eukaryotes than bacteria. Interestingly, whereas bacterial cells contain a single FtsZ, many archaea encode multiple homologs, some of which are more closely related to tubulin.

We found that two of the eight tubulin/FtsZ homologs present in the model archaeon Haloferax volcanii are essential for normal cell division. However, FtsZ1 and FtsZ2 had different roles in cell division. By developing GFP-tagging approaches for this species, combined with super-resolution and time-lapse fluorescence microscopy, we revealed a dynamic pattern of protein localization during cell division in which planes of cell division are established orthogonally in successive cell cycles.

The remaining six tubulin-like proteins in H. volcanii were not required for cell division. They are members of a distinct family, widespread in the euryarchaea, that show greater similarity to eukaryotic tubulins. These previously uncharacterized proteins, named CetZ, were found to control cell shape transitions in H. volcanii cells, from the common discoidal cell type to an elongated rod-shaped form required for cell motility. In vivo studies of CetZ function and cellular localization, using super-resolution microscopy and cryo-electron tomography, have provided further insight into how these proteins might control cell shape. This new function in prokaryotes is reminiscent of tubulin's role in controlling eukaryotic cell structure. Together with our crystal structures of CetZ proteins in monomer and proto-filament forms, these findings suggest that the CetZ protein family may resemble an early intermediate in the evolution of the tubulin cytoskeleton.