Review TRENDS in Cell Biology
The push and pull of the bacterial
cytoskeleton
Natalie A. Dye1,2 and Lucy Shapiro2
1
Department of Biochemistry, Beckman Center, Stanford University, Stanford, CA 94305, USA
2
Department of Developmental Biology, Beckman Center, Stanford University, Stanford, CA 94305, USA
A crucial function for eukaryotic cytoskeletal filaments is
to organize the intracellular space: facilitate communi-
cation across the cell and enable the active transport of
cellular components. It was assumed for many years that
the small size of the bacterial cell eliminates the need for
a cytoskeleton, because simple diffusion of proteins is
rapid over micron-scale distances. However, in the last
decade, cytoskeletal proteins have indeed been found to
exist in bacteria where they have an important role in
organizing the bacterial cell. Here, we review the pro-
gress that has been made towards understanding the
mechanisms by which bacterial cytoskeletal proteins
influence cellular organization. These discoveries have
advanced our understanding of bacterial physiology and
provided insight into the evolution of the eukaryotic
cytoskeleton.
Bacterial cytoskeletal proteins
Cytoskeletal elements have been identified in prokaryotes
based on structural and functional homology to eukaryotic
proteins (Table 1 and Ref. [1]). Although there is virtually
no primary sequence similarity between prokaryotic and
eukaryotic cytoskeletal elements, prokaryotic proteins
with actin- and tubulin-like folds have been found. Many
of these proteins have been shown to polymerize in vitro in
a nucleotide-dependent manner. Furthermore, genetic and
cell biological data suggest that, in vivo, these proteins
share many of the functions of eukaryotic cytoskeletal
proteins: they are involved in cellular organization,
division and maintenance of cell shape. In addition to actin,
tubulin and intermediate filament-like proteins, a class of
proteins, the MinDParA superfamily, exists, which, in
bacteria, appears to have cytoskeletal functions (Box 1).
Although there are eukaryotic ATPases with similar struc-
tures and sequences to those of MinDParA proteins, the
ability to polymerize in vivo and in vitro seems limited to
the prokaryotic homologs.
Given that passive diffusion alone can enable cellular
components to sample a small bacterial cell rapidly, it has
been somewhat surprising to find that many of the bac-
terial cytoskeletal proteins are thought to be involved in
positioning proteins and DNA actively (Table 1). Instead of
listing what is known about the genetic phenotypes or
the polymerization properties of each individual bacterial
cytoskeletal protein (reviewed in Ref. [1]), we will here
Corresponding author: Shapiro, L. (shapiro@stanford.edu).
Available online 16 April 2007.
www.sciencedirect.com 0962-8924/$ see front matter 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tcb.2007.03.005
Vol.17 No.
review the general mechanisms that are emerging for how
cytoskeletal proteins in bacteria influence cellular organ-
ization.
A push in the right direction
The most basic way to influence the localization of cellular
components is to physically move them through the cyto-
plasm to a specific location. In eukaryotic cells, there are
motor proteins that directly transport vesicles, mRNA and
proteins along tracks of actin or tubulin. However, actin
and tubulin themselves can also function as motors to
propel objects through the cytoplasm (Box 2). In bacteria,
the plasmid-encoded actin homolog, ParM, is thought to
force actively two clusters of plasmid DNA apart, using its
ability to polymerize (Figure 1a) [25].
The plasmid R1 exists in low copy number in the
Escherichia coli cytoplasm and would be quickly lost from
the population without an active mechanism for segregat-
ing the DNA into both daughter cells at division. There are
three components encoded by the plasmid that are dedi-
cated to its partitioning: the actin-like ParM, the DNA-
binding protein ParR, and the centromer-like parC DNA
region [6]. These three components form a complex that is
necessary and sufficient for the segregation of the DNA in
vivo [57]. The regulation of par locus expression and the
integration of plasmid replication with the host cell cycle
are reviewed elsewhere [8].
In the cell, plasmid molecules cluster together so that
the DNA appears as tight foci upon labeling [8,9]. Early in
the cell cycle, there is only one focus, which colocalizes with
foci of ParM and ParR at midcell [5,9]. As the cell cycle
progresses, the plasmid is replicated by host machinery
and split into two foci that move to opposite poles
before division. As the plasmid foci move, they appear to
be connected by a line of ParM [5,9]. The formation of these
ParM filaments in vivo requires the ParRparC complex
and is essential for plasmid segregation [10]. Additionally,
these filaments must be dynamic. A mutant ParM with
altered ATPase activity still forms filaments, but they
often inhibit cell division and abolish plasmid segregation
[7,9,10].
In vitro, ParM forms filaments with strikingly similar
ultrastructure to eukaryotic actin filaments [10,11]. In
vitro-filament formation can be stimulated by the complex
of ParR bound to parC [10]. This result was first inter-
preted to mean that ParR accelerates the nucleation of
ParM polymerization on DNA, because the nucleation step
is a kinetic hurdle in the polymerization of eukaryotic
240 Review TRENDS in Cell Biology Vol.17 No.5
Table 1. Functions and mechanisms of selected bacterial cytoskeletal proteinsa
a
The proteins listed above have been categorized according to their homology to eukaryotic cytoskeletal proteins. In white are actin homologs, in yellow, the tubulin homolog;
in green, intermediate filament homolog; in orange, the MinDParA superfamily, which does not have any counterpart in the eukaryotic cytoskeleton.
b
The references listed provide recent insights into the molecular mechanism of these proteins in contributing to cellular organization. More information on the bacterial
cytoskeletal elements that are not discussed here can be found in a separate recent review [1].
actin. However, when the rate of ParM nucleation was
directly measured in vitro, it was found to be 300 times
faster than that of eukaryotic actin [2]. The critical concen-
tration for polymerization of ParM in vitro was also found
to be much lower than its in vivo cellular concentration
Box 1. The MinDParA family of bacterial-specific
cytoskeletal proteins
In bacteria, members of a superfamily of Walker ATPases have
cytoskeletal properties and regulate the localization of both DNA
and protein. Members of this family all share the deviant Walker A
motif, GXGGXHK[TS], within the P-loop ATP-binding pocket [66].
MinD and ParA are two members of this family that were
characterized early and represent two groups distinct in sequence
and function. MinD regulates the position of the cytokinetic FtsZ-
ring by controlling the localization of a FtsZ inhibitor, MinC
(reviewed in Refs [1,27,37]). The ParA subgroup functions in the
segregation of DNA [64]. Three subclasses of the ParA group can be
identified, based on protein sequence: chromosomal and plasmid
Type Ia and Ib [65]. Although it shares its Par name with ParM,
ParA does not resemble actin in structure.
To date, five members of the MinDParA superfamily have been
shown in vitro to polymerize into filaments in a nucleotide-
dependent manner: MinD (E. coli), Soj (B. subtilis), ParA (plasmid
pB171), ParF (plasmid TP228), and SopA (F plasmid) [23,24,63,67
69]. All but Soj were shown to form long, thin protofilaments
assembled into large, bundled structures with a frayed appearance
at one end. Soj polymers do not resemble these bundled structures,
and it is not yet known whether this difference is due to an inherent
difference between the homologs or variation in the experimental
conditions.
In vivo, MinDParA homologs tend to form large-scale filamen-
tous structures that follow a helical path in the cell, often with
oscillatory dynamics [2224,55,7072]. E. coli MinD, for example,
forms a helix at one cell pole that dissociates and reforms at the
opposite pole approximately every 20 s, a process dependent on a
regulatory protein, MinE [55,72]. Mutations that affect nucleotide
hydrolysis do not prevent the formation of such helical structures
but do affect their dynamic behavior.
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[24,10]. Finally, ParM filaments in vitro were found to be
unstable, constantly alternating between phases of
elongation and rapid disassembly, a process called dynamic
instability [24]. In light of these in vitro findings, it now
seems likely that ParRparC regulates ParM filament
stability, rather than nucleation. These data suggest an
in vivo model (Figure 1a) whereby ParM filaments are bound
at both ends to two different plasmid clusters through ParR,
which protects them from their inherent instability and
enables them to elongate to sufficient lengths to separate
the plasmids to opposite ends of the cell [24]. The polymer-
ization of ParM in-between ParR would provide the force
required to separate the plasmid clusters (Box 2) [24].
Recently, this model was confirmed with an in vitro
reconstitution of plasmid segregation with purified ParM,
ParR and parC [3]. In the presence of ATP and ParR, ParM
forms dynamic astral filaments on the surface of the parC-
coated microspheres. In addition, it is possible to see ParM
filaments connecting two or more beads, forming a spindle-
like structure similar to that observed in vivo, which
elongates to push the beads apart. It is even possible to
witness search and capture events, where filaments
extending off of the surface of one bead reach out and
contact a neighboring bead. ParM filaments in between
beads then elongate as the beads separate from one
another (Box 2).
This in vitro reconstitution experiment demonstrates
that ParM polymerization, coupled to ParRparC, can
directly exert force on an object, mirroring actin polymer-
ization driving the intracellular movement of Listeria
monocytogenes and whole cell motility in eukaryotic cells
(Box 2) [12]. Furthermore, the reconstitution experiments
provide additional support for a model in which ParR-
binding to ParM stabilizes the filaments in-between two
segregating pieces of DNA. Long filaments of ParM were
 Review TRENDS in Cell Biology
Box 2. Force generation by polymerization
The polymerization of a cytoskeletal protein can be used to move a
load through a mechanism referred to as thermal or Brownian
ratcheting (reviewed in Ref. [12]). Spontaneous elongation of a
polymer occurs when the free energy of the subunit in its polymer
state is lower than the free energy of the subunit in its monomer
state, which is true above a certain critical concentration (Ccrit). If the
polymer is attached to an object, for example another protein or
piece of DNA, the energy that is released upon polymerization can
be used to displace the object in the direction of polymerization. The
maximum amount of force a polymer can exert is related to the
thermodynamics of its polymerization:
    gation [14]. Recent evidence from the bacterium Vibrio
kBT C 
F max ln [I]
d C crit
In the above equation (Equation I), kB is the Boltzmanns constant;
T is the absolute temperature; d is the distance the object is moved
by the insertion of a single subunit; [C] is the monomer concentra-
tion; and Ccrit is the critical concentration for polymerization, which
is normally equal to the ratio of koff to kon, the rate constants for the
depolymerization and polymerization, respectively.
We can now estimate the maximum force that can be generated
by ParM polymerization, given the measured parameters of
d = 2.45 nm (1/2 the diameter of a monomer, because ParM is a
double stranded polymer) [11], T = 25 8C, Ccrit of ATP-bound
ParM = 0.6 mM (ATP is in excess in the cell) [2,4], and [C] = 2.3 mM
(steady-state concentration of monomer) [2,3]. These values predict
that single filaments of ParM can exert up to 2.3 pN of force.
Interestingly, the nucleation rate of ParM is rapid and the critical
concentration of ATP-bound ParM (ATP-ParM) is much lower than
its cellular concentration of 1214 mM [10]. Therefore, much of the
ParM in the cell should in theory be in filament form at steady state
and unable to provide any force. In fact, in eukaryotic cells, actin is
also present at concentrations well above its critical concentration;
however, the presence of multiple depolymerizing proteins and
monomer-sequestering proteins in the cell maintains a high steady
state concentration of monomers.
In the case of ParM, however, there is no need for other proteins
to regulate polymerization because the filaments themselves exhibit
dynamic instability. Once hydrolysis of ATP occurs, the ParM
filament is unstable. This is demonstrated by the fact that the
critical concentration of ADP-bound ParM (ADP-ParM) is at least two
orders of magnitude larger than the ATP-ParM, meaning that the off-
rate of monomers from the filament is much faster than the on-rate
[2]. The balance between rapid nucleation of ATP-ParM and rapid
depolymerization of ADP-ParM upon hydrolysis results in dynamic
instability, which maintains a steady-state monomer concentration
of 2.3 mM [2,3]. The in vitro reconstitution of the ParM-mediated
movement of DNA enabled the direct demonstration of the
requirement of dynamic instability to power force generation [3].
With a steady-state concentration of monomers above the critical
concentration for ATP-ParM, polymerization can be coupled to the
generation of force. The only protein required for the coupling is
ParR, which selectively stabilizes the ParM filaments on DNA.
Therefore, the kinetic parameters of ParM polymerization are aptly
tuned so that the ParMParRparC complex can function in the
absence of other cellular factors, a property that is undoubtedly
favorable for a plasmid-encoded system.
only observed in-between two beads bound by ParR. If the
spindle is severed with laser ablation, the newly generated
free end of the filament, which is not bound to ParR, rapidly
depolymerizes [3].
It is not yet known whether other plasmids use a
partitioning mechanism similar to the ParM-pushing
mechanism. However, a newly discovered actin homolog
from Bacillus subtilis, AlfA, which is required for the
segregation of plasmid pLS32, resembles ParM in its
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Vol.17 No.5 241
intracellular localization pattern and dynamics [13]. This
result suggests that AlfA might also be able to push
plasmids through the cytoplasm like ParM, although this
hypothesis has yet to be tested.
A mitotic-like pull
Just as polymerization can generate a pushing force,
depolymerization can generate a pulling force. In eukar-
yotic cells, for example, the energy released upon depoly-
merization of microtubules can be harnessed by a complex
of proteins attached to chromosomes, driving their segre-
cholerae suggests an analogous pulling mechanism might
exist in prokaryotes as well [15]. V. cholerae has two
chromosomes, each encoding its own partitioning genes
and exhibiting distinct dynamic behaviors upon segre-
gation [16,17]. The mechanism of segregation of chromo-
some II is not yet known, but recent work indicates that
chromosome I might be pulled to the pole by a ParA
homolog (Figure 1b) [15]. Although they are similarly
named (Par referring to a role in partitioning), ParA
and ParM are different at both the sequence and structural
levels (Box 1).
At the beginning of the cell cycle, ParA of chromosome I
(ParAI) localizes to the oldest pole of the cell with a DNA-
binding protein ParB and the origin of replication [15].
ParAI is also found in the opposite half of the cell in a haze
that can be resolved into filamentous structures with
deconvolution microscopy. Once the origin duplicates,
one copy stays at the old pole, along with foci of ParB
and ParAI. The other ParBorigin complex moves across
the cell at the edge of the filamentous ParAI structure. As
the migration of the chromosome progresses, the ParAI
zone shrinks towards the new pole, finally condensing into
a polar focus.
In the absence of ParAI, the origin does not exhibit the
same dynamic behavior [15]. The two ParBorigin com-
plexes can be seen floating in the cytoplasm, no longer
restricted to the pole. This data suggests that not only does
ParAI have a role in directing one of the origins to the new
pole, but also in keeping the other origin at the old pole.
Interestingly, in the absence of ParAI, the two origins are
still able to move apart from one another, but they do so
inefficiently and bidirectionally, rather than asymmetri-
cally as in the wild-type cells. It is possible that a parti-
tioning mechanism that directs chromosome II movement
is able to compensate partially for the absence of ParAI.
Unlike ParM, ParAI does not localize in-between the
two separating DNA loci; instead it localizes in-between
one of the duplicated loci and the new pole of the cell
(Figure 1). It seems clear, therefore, that ParAI and ParM
act through distinct mechanisms. In V. cholerae, the data
are consistent with a model in which ParAI is pulling the
duplicated origin in, toward the new pole, similarly to the
way in which microtubules direct the motion of chromo-
somes in eukaryotic cells. It has not yet been shown that
this particular ParA homolog can self-associate into fila-
ments in vitro (Box 1), but it has been shown to make
filamentous structures in vivo. Additionally, mutations in
the ATPase domain of ParAI abolish its dynamic behavior
and its ability to position the origin, which is consistent
242 Review TRENDS in Cell Biology Vol.17 No.5

Figure 1. Cytoskeletal-mediated movement of DNA in bacteria. Schematics of the in vivo segregation dynamics, on the left, and a molecular model, on the right, are
presented for two distinct cytoskeletal partitioning mechanisms. (a) The actin-like ParM forms a bundle of filaments in-between duplicated plasmids that elongates as
plasmids segregate to the poles. These filaments are bound through the DNA-binding protein ParR (green) to a specific site on the plasmid, parC. Insertion of ATP-
monomers (red) at the growing tip of filaments is proposed to exert force on the plasmids, separating the two copies (in the direction of the arrows). ADP-monomers (blue)
accumulate in the filament, owing to its hydrolysis activity, making the filament unstable and subject to rapid depolymerization. When bound to the DNA through ParR,
however, the filaments are presumably protected from depolymerization. (b) V. cholerae ParAI (yellow) forms filaments that extend from the cell pole to attach to an origin
proximal region of chromosome I as it is segregating. Again, a DNA-binding protein, ParB (green), appears to mediate the interaction between ParA and the DNA. As the
migration of the chromosome continues, the ParAI filaments shrink toward the new pole (in the direction of the arrow). This pattern is consistent with a model that ParAI
exerts force on the DNA, pulling it to the pole, although this mechanism has not been confirmed.

with a role for depolymerization in mediating segregation
[15].
Visualization of ParAI filamentous structures in vivo
using high resolution electron microscopy would confirm
the existence of a cytoskeletal structure and help clarify
the mechanism of chromosome movement. Interestingly,
in Caulobacter crescentus, clusters of filaments of unknown
protein composition have been detected, tethered to the
pole of the cell [18]. C. crescentus and V. cholerae both
localize a chromosomal origin to the pole [16,17,19].
Additionally, C. crescentus ParA is essential for chromo-
some segregation and shares considerable homology with
V. cholerae ParAI [20]. Therefore, it is possible that these
two ParA homologs use similar mechanisms and that the
electron micrographs have captured the C. crescentus ParA
in the act of separating the chromosome. To confirm this
hypothesis, it will be necessary to see if the polar filaments
are missing in a ParA-depleted C. crescentus strain.
Recently, a ParA homolog in Rhodobacter sphaeroides,
PpfA, was found to be required for the segregation of
clusters of a chemotaxis protein, TlpT [21]. This discovery
is the first example of a ParA homolog mediating the
segregation of a protein, rather than DNA. The mechanism
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of this segregation is unknown. It is likely to be distinct,
however, from that of V. cholerae ParAI, given their differ-
ent localization patterns. TlpT clusters segregate to the
quarter-cell positions, rather than at the poles [21]. The
pattern of segregation actually resembles that of V. cho-
lerae chromosome II [16,17], in addition to that of certain
plasmids in E. coli, such as F and pB171, which are also
regulated by related by filament-forming ParA homologs
[2224].
Dynamic scaffolding
Cytoskeletal proteins do not have to physically move
proteins or DNA through the cytoplasm to influence cellular
organization. A higher order cellular structure formed by
cytoskeletal proteins can act as a scaffold to direct the
localization of other cellular components. Just one of many
possible examples from eukaryotic cells is the microtubule
network in plants, which forms a scaffold for cell wall
synthesis, directing the placement of the synthetic enzymes
and the orientation of the cellulose microfibrils [25].
Theoretically, cells can form scaffolds with anything
capable of forming a higher order structure. The polymer-
ization of a cytoskeletal protein, however, is coupled to
 Review TRENDS in Cell Biology
nucleotide hydrolysis. Therefore, the assembly and
disassembly of cytoskeletal scaffolds is rapid and can be
easily regulated with modulators of polymerization. This
dynamic property enables the structure to be intimately
integrated with the cell cycle and to be responsive to its
intracellular environment. In bacteria, there are at least
three examples of such dynamic cytoskeletal scaffolds.
FtsZ organizing the division apparatus
The tubulin homolog, FtsZ, is a scaffold for several proteins
involved in cytokinesis. Its filaments form a ring-like struc-
ture that defines the division plane [26]. In the absence of
FtsZ, all of the other proteins involved in division fail to
localize correctly and the cell cannot initiate constriction
(reviewed in Refs [1,27]). This Z-ring structure is stabilized
and bound to the membrane largely by the protein FtsA,
another actin homolog [2830]. Numerous different mol-
ecules are then recruited to this site. In E. coli, FtsA is
thought to recruit downstream effectors directly to the site of
the FtsZ ring [27,31,32], whereas in B. subtilis, the newly
discovered proteins SepF and YlmF are also involved in the
recruitment process [28,33,34]. FtsZ might also be directly
exerting force on the membrane during constriction,
although there is currently little direct evidence to support
this idea.
The FtsZ ring, perhaps more than any other cytoskeletal
structure, demonstrates the importance of dynamic beha-
vior in a scaffold. Photobleaching experiments have shown
that the Z-ring of E. coli and B. subtilis is continually
remodeling with a half-time of 89 s [35]. Additionally,
low levels of filaments can be seen rapidly traversing the
cell along a helical path [36]. Mutations that affect the
GTPase activity of FtsZ alter its dynamic behavior and do
not fully support cytokinesis [35]. Its dynamic behavior
enables FtsZ to sample the cell quickly and to position itself
optimally between the replicated chromosomes. Specific
mechanisms for integrating Z-ring assembly with chromo-
some segregation in E. coli, B. subtilis and C. crescentus have
been characterized [27,37,38]. Although each organism
accomplishes this task differently, they all link a sensor
for the intracellular position of DNA to a regulator of FtsZ
polymerization. For example, in C. crescentus, the origin of
replication recruits a direct inhibitor of FtsZ polymerization,
MipZ [38]. When the origins duplicate and segregate to the
poles, MipZ travels with them and FtsZ is forced to poly-
merize at midcell, the area of lowest inhibitor concentration.
This mechanism ensures a dynamic coupling between
chromosome segregation and cytokinesis.
The FtsZ ring is also responsive to variations in
intracellular conditions. In B. subtilis, the initiation of
sporulation causes the Z-ring to be moved from a midcell
to a polar site [39]. In E. coli, DNA damage induces the
expression of a specific FtsZ inhibitor, SulA, that arrests
cell division [40]. Again, the rapid turnover of FtsZ fila-
ments enables these responses to occur within seconds.
MreB and MreC directing helical cell wall growth
The actin homolog MreB (and MreB-like proteins in B.
subtilis), in rod-shaped bacteria, forms a dynamic helical
scaffold that controls the localization of cell wall growth
[4143]. Enzymes involved in cell wall synthesis and
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Vol.17 No.5 243
peptidoglycan precursor molecules localize in the cell
following a helical pattern that is similar to that of MreB
[4146]. In the absence of MreB, these enzymes and
precursors are incorrectly localized, resulting in misshapen
cells [4146]. Therefore, it has been suggested that MreB
creates helical tracks onto which the cell wall machinery
localizes, perhaps in a similar fashion to the way plants use
the microtubule cytoskeleton as tracks for cellulose syn-
thesis [25].
Though the mechanism by which MreB controls cell wall
growth is not fully understood, it is known to involve
another helical scaffold composed of the MreC protein,
whose gene lies in the mreB operon [4548]. Unlike MreB,
MreC is not an actin homolog, nor does it resemble any
other known protein, yet, in the cell, it is able to localize in a
helical pattern that resembles that of MreB [4548]. In C.
crescentus, this MreC spiral resides in the periplasmic
space and is non-overlapping with the MreB pattern
[45,46]. MreC is required for the localization of an enzyme
for cell wall synthesis, Pbp2, in addition to several outer
membrane proteins, suggesting that it might have a gen-
eral role in the organization of the periplasmic and outer
membrane compartments [45,46].
Like FtsZ, the MreB structure inside cells has been
shown to exhibit a rapid dynamic behavior that is probably
due to its ability to hydrolyze nucleotide [4953]. C. cres-
centus MreB undergoes regulated transitions in its cellular
localization, making a helical structure early in the cell
cycle and then reorganizing into a ring structure positioned
at the division plane later in the cell cycle. [43,54]. The
mechanism and function of this large-scale reorganization
is not known. It could conceivably be involved in a switch
between elongation and division-specific phases of cell wall
growth. In E. coli, MreB is also able to form a variety of
helical and ring structures, but a similar coordination with
the cell cycle has not been observed [55].
MamK lining up magnetosensing organelles
A different actin-like protein, MamK, forms a linear scaffold
in magnetotactic bacteria [56]. These bacteria form crystals
of either Fe3O4 or Fe3S4 within membrane-bound clusters
that line up along the long axis of the cell (reviewed in Ref.
[57]). Using both cryoelectron tomography and fluorescence
microscopy, MamK can be seen forming filaments right
under the magnetosensing organelles in Magnetospirillum
magneticum [56]. In the absence of MamK, no filaments are
observed, the organelles disperse throughout the cytoplasm
or aggregate, and the organism is no longer magnetotactic
[56]. The polymerization of MamK has not yet been studied
in vitro. In addition, its dynamic behavior in vivo is only
beginning to be investigated [58]. Presumably the structure
must be able to disassemble at division to enable separation
of the two daughter cells, but this process has not yet been
observed in live dividing cells. It is also not known whether
MamK is involved in segregating the magnetosensing orga-
nelles at division.
Concluding remarks
Both prokaryotes and eukaryotes seem capable of using
cytoskeletal polymers to actively and dynamically organize
their intracellular space. Moreover, archeal homologs of
244 Review TRENDS in Cell Biology Vol.17 No.5
FtsZ and MreB have been identified, although little is
known about their function in vivo. Nonetheless, the pre-
sence of this activity in eukaryotic and prokaryotic organ-
isms argues that there is a fundamental requirement for
dynamic polymers in cellular life and ancient mechanisms
of polymer motors and scaffolds.
Dynamic cytoskeletal polymers were thought to be
vitally important to the evolution of eukaryotic cells,
enabling them to grow in size by orders of magnitude
and accomplish more complex tasks than the morphologi-
cally simpler bacteria and archaea [59]. Now that it has
become clear that prokaryotic organisms have cytoskeletal
proteins that are fundamentally similar in structure and
activity to eukaryotic actin and tubulin, how have eukar-
yotes evolved a cellular biology that is so much more
complex?
Currently, there is not enough known about the bacterial
cytoskeleton to answer definitively this question. As it
stands, there does seem to be a difference in the functional
diversity between eukaryotic and prokaryotic cytoskeletons.
Eukaryotic actin and tubulin are responsible for the specific
localization of thousands of molecules and are involved in
many different mechanical processes. To accomplish this
feat, eukaryotes have evolved a huge repertoire of binding
partners and regulatory proteins for actin and tubulin. By
contrast, prokaryotic cytoskeletal elements have so far been
shown to be specialized for one particular function, for
example the segregation of a particular DNA locus or the
localization of one particular protein. MamK, for example, is
only involved in lining up the magnetosensing clusters and
cannot substitute for E. coli MreB in cell wall synthesis
[58,60].
The one key exception to this observation is C. crescentus
MreB, which has been implicated in chromosome segre-
gation, protein localization and cell wall synthesis
[43,45,46,53,54,61]. There is not yet sufficient evidence to
show that MreB has a direct role in all these processes. The
effect MreB has on polar positioning of proteins might be
secondary to its role in directing cell wall growth [60]. It will
be important in the future to determine whether MreB is
able to participate directly in more than one cellular process
and, if so, to use different types of mechanisms.
The ability to use the same cytoskeletal proteins in
many different processes might have been crucially
important in the evolution of the complex eukaryotic
organisms that we see today [59]. Motor proteins that
move along cytoskeletal filaments, such as myosin and
kinesin, might have also been key in that development.
Such proteins have not yet been found in bacteria and
might not exist. They might have been a recent develop-
ment that evolved to improve the efficiency of intracellular
motility and organization and thereby enable more com-
plex functions [59].
Acknowledgements
We thank Erin Barnhart, Matt Footer, Ethan Garner, Erin Goley,
Antonio Iniesta, Kinneret Keren, Julie Theriot and Esteban Toro for
critical reading of the manuscript and inspiring discussions.
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