634The structural and functional resemblance between thebacterial cell-division protein FtsZ and eukaryotic tubulin wasthe first indication that the eukaryotic cytoskeleton may have aprokaryotic origin. The bacterial ancestry is made even moreobvious by the findings that the bacterial cell-shape-determining proteins Mreb and Mbl form large spirals insidenon-spherical cells, and that MreB polymerises in vitro intoprotofilaments very similar to actin. Recent advances inresearch on two proteins involved in prokaryotic cytokinesisand cell shape determination that have similar properties to thekey components of the eukaryotic cytoskeleton are discussed. AddressesMedical Research Council Laboratory of Molecular Biology, Hills Road,Cambridge CB2 2QH, UK *e-mail: [email protected] Opinion in Microbiology 2001, 4:634–6381369-5274/01/$ — see front matter© 2001 Elsevier Science Ltd. All rights reserved.AbbreviationsF-actin filamentous actinFtsZ filamentous temperature-sensitive protein ZGTP guanosine triphosphateMre murein cluster eMSP major sperm proteinMT microtubuleIntroductionDespite their apparent internal simplicity, bacteria undergodivision at a remarkable speed and with a high precisionthat requires a dynamic intracellular organisation. Untilrecently, the lack of a cytoskeleton, which for eukaryotes isindispensable to complete mitosis and cytokinesis success-fully, has been one of the defining features of prokaryotes.Besides mitosis, the eukaryotic cytoskeleton is vital formaintenance of cell shape, and for phagocytosis, organellemovement and locomotion. At least some of these processesoccur in bacteria as well, but little is known about theirregulation. Recent results indicate that bacteria containproteins that are similar to cytoskeletal elements ineukaryotic cells. In this review, we will shed light on twokey components of the eukaryotic cytoskeleton that haveremarkable similarities to proteins involved in prokaryoticcytokinesis and cell shape determination.Eukaryotic cytoskeletonIn eukaryotes, cell shape and the organisation of directedmovements depend on the cytoskeleton. The operation ofthe eukaryotic cytoskeleton is based on microtubules andfilamentous actin that work together. Both tubulin andactin couple intrinsic nucleotide triphosphate hydrolysis topolymer formation [1], whereas passive structures suchas intermediate filaments are dependent on accessoryproteins for polymer formation [2]. Intermediate filamentsare not evolutionarily conserved, hence, in this review, weshall focus on tubulin and actin and their putativehomologues in prokaryotic cells.The eukaryotic cytoskeleton is not a static structure. Thepolymers of the cytoskeleton are highly dynamic, allowingthe cytoskeleton to rapidly re-organise. Owing to thepolymerisation dynamics, the polymers have the potentialto carry out mechanical work, either via treadmilling(assembly at one end and dissociation at the other end) orvia dynamic instability (stochastic changes in their length)[3,4]. Both actin and tubulin require nucleotides for theirpolymerisation, the hydrolysis of which destabilises thepolymers. This is in contrast to polymer formation ofbacterial flagellin and the tobacco mosaic virus (TMV) coatprotein [1]. Another eukaryotic filament-forming protein ismajor sperm protein (MSP). Although MSP does not showany sequence homology to actin, it replaces actin in thesperm of certain nematodes [5]. The mobility of those cellsis powered by dynamic polymerisation of MSP. (The exactmechanism of MSP polymerisation in vivo is not known.In vitro, ethanol was used to induce reducible polymerisation,and experiments are underway that show that accessoryproteins may be involved in the control of MSP polymeri-sation.) The structure elucidation of the 14 kDa Ascarissuum α-MSP protein showed that it is a member of theimmunoglobin superfamily of proteins [6]. There is noobvious candidate for an MSP-like protein in bacteria.Dynamic polymerisation is only one mechanism by whichactin and tubulin achieve some of their specific functions.The polar nature of microtubules and actin filamentscontrols the direction of motor proteins and hence enablesthe spatial organisation of the cell. Microtubules (MTs) arethought to be involved in long-range transport of organelles[7]. MTs serve as a track on which motor proteins, such asthose of the kinesin and dynein superfamilies, carry theircargo. They form the mitotic spindle that segregateschromosomes and determine the plane of cleavage. Innon-dividing cells, MTs are involved in the organisation ofthe cytoplasm, in positioning the nucleus and variousorganelles, and in the formation of flagella and cilia [8].Filamentous actin (F-actin) forms the track for myosinmotors and is used for local transport [3,9], as well as forcytokinesis and motility.Tubulin and FtsZMTs are hollow cylinders (25 nm wide) that normally consistof 13 parallel filaments. Each filament is a longitudinalarray of heterodimers of α- and β-tubulin. Both tubulinsubunits bind the nucleotide guanosine triphosphate(GTP), but only GTP in β-tubulin is hydrolysed, resultingin destabilisation of the filament. The α- and β-tubulinsubunits are 50% identical to each other in sequence. TheBacterial ancestry of actin and tubulinFusinita van den Ent, Linda Amos and Jan Löwe*Bacterial ancestry of actin and tubulin van den Ent, Amos and Löwe 635three-dimensional structure of tubulin, determined byelectron crystallography, reveals remarkable structural sim-ilarity to a bacterial cell-division protein called filamentoustemperature-sensitive protein Z (FtsZ) [10,11]. Despitelow sequence similarity, the three-dimensional structuresof tubulin and FtsZ are extremely similar. Both tubulinand FtsZ have a Rossmann fold in their amino-terminalpart, with the characteristic parallel β-sheet of six strands,and co-ordinate the nucleotide (GTP) in a correspondingmanner (Figure 1). The resemblance extends to thefunctions of tubulin and FtsZ [12]; both proteins exhibitGTP-dependent polymerisation into filamentous structures.GTP hydrolysis regulates the dynamic behaviour of FtsZfilaments and microtubules [8,13,14]. In vitro, tubulin andFtsZ form tubes and sheets that consist of parallel orantiparallel