What Does it Take To Divide
a Bacterial Cell?
Specialized cytokinesis proteins form a membrane-spanning
apparatus that gradients target to the midpoint of bacterial rods
William Margolin
ne of the most daunting tasks for
any cell is to divide its components
evenly into two daughter cells. The
last steps of this process, called cytokinesis, are crucial for any type
of cell undergoing growth or differentiation,
and bacteria are no exception. Largely through
combined use of fluorescent protein tags, molecular genetics, and genomics, we now know that
a number of proteins dedicated to cytokinesis
are recruited to the site of cell division in many
bacteria, where they assemble into a molecular
machine that spans the cytoplasmic membrane.
Researchers recently developed a mechanism
explaining how the division site in cells is selected. Furthermore, two of the proteins involved in cytokinesis are homologs of eukaryotic cytoskeletal proteins. As a result, these
findings carry implications for all of cell biology.
O
Summary
• Two widely distributed bacterial proteins, FtsZ
and FtsA— homologs of tubulin and actin, respectively—are key components of bacterial
cytokinesis.
• Chemical gradients are key to directing the cytokinesis apparatus to the midpoint of rodshaped bacterial cells.
• The particular proteins responsible for regulating cell division vary from one bacterial species
to another; moreover, other factors affecting
growth rate can affect this process.
• Because the cytokinesis apparatus of bacterial
cells is overbuilt and contains redundancies,
cells can withstand the loss of some components.
Despite knowing many components of the
cytokinesis machinery from several bacterial
species, however, the mysteries of how it works
are far from solved. What are the precise roles of
the components, which are core, and which
accessory? What are the cell cycle signals that
trigger its formation, constriction, and disassembly? What regulates the switch from cell
wall elongation to growth of the division septum? Do cocci mainly grow by their division
septum, thereby bypassing the need for this
switch? Progress will depend on improved technologies such as cryotomography and singlemolecule methods for visualizing the structure
and dynamics of this cellular machinery at
higher resolution. Meanwhile, investigating this
complex cellular process in a diverse set of microorganisms contributes to our growing understanding.
Tubulin Homolog Plays Key
Role in Bacterial Cell Division
For years, biologists thought that bacteria
lack a cytoskeleton and cytoskeletal proteins. However, two widely distributed bacterial cell division proteins, FtsZ and FtsA,
appear to be distant homologs of tubulin
and actin, respectively. Although microtubules and actin filaments in eukaryotes generally do not interact directly, FtsZ and
FtsA do so, together ensuring the integrity
of the cell division machine. Of the two,
FtsZ is the more highly conserved and functions at a very early stage. FtsZ self-assembles into a membrane-associated ring at
what becomes the division site between segregated chromosomes (Fig. 1), binding GTP
William Margolin is
a Professor in the
Department of Microbiology and Molecular Genetics,
University of Texas
Medical School,
Houston.
Volume 3, Number 7, 2008 / Microbe Y 329
FIGURE 1
Stages in cytokinesis are diagrammed at the left, with nucleoids shown as red ovals.
Inset: Immunofluorescence micrograph of E. coli cells stained with DAPI (red) for
nucleoids and Alexa-488-labeled anti-FtsZ (green) to highlight FtsZ rings.
and forming 5-nm-wide protofilaments that resemble the protofilaments made by tubulin
within a microtubule.
In rod-shaped cells such as Escherichia coli
or Bacillus subtilis, this site is at the middle,
whereas in cocci it is at the point of widest diameter and may be either parallel to the previous
division, as in chain-forming streptococci, or perpendicular, as in Neisseria or Deinococcus species.
The FtsZ ring consists of a loose assemblage of
FtsZ protofilaments near the cytoplasmic membrane, according to Grant Jensen at the California
Institute of Technology in Pasadena and collaborators. They reached this conclusion through an
analysis based largely on electron tomography, a
relatively new imaging technique that visualizes
native structures in cells without relying on
chemical fixation or staining.
Although the FtsZ ring appears stable under
330 Y Microbe / Volume 3, Number 7, 2008
typical fluorescence microscopy conditions, it is highly dynamic (Fig. 2). According to David Anderson and Harold
Erickson at Duke University, Durham,
N.C., and their collaborators, the turnover rate of FtsZ subunits within these
protofilaments is on the order of 8 –9
seconds, and only 30% of the cellular
FtsZ is in the FtsZ ring. Turnover depends on hydrolysis of GTP molecules.
Consistent with these dynamics,
Phoebe Peters, Elizabeth Harry,
and their colleagues at the University of
Technology in Sydney, Australia, as
well as Swapna Thanedar in my laboratory, find that fluorescent FtsZ moves
rapidly within spiral structures that
span the length of the bacterial cell.
These FtsZ spirals are even more pronounced in newborn cells before an
FtsZ ring forms, probably because they
contain most of the cellular FtsZ.
Together, these results indicate that
FtsZ forms a membrane-associated cytoskeletal array, reminiscent of interphase microtubules in eukaryotes, and
that it is in equilibrium with the ring.
Other bacterial proteins that associate
with the membrane also localize as spiral arrays, including the bacterial actin
homologs MreB and Mbl that are involved in regulating cell wall growth, as
well as the MinD protein.
Negative Spatial Regulators Direct
FtsZ to the Division Site
How is the FtsZ ring targeted to the middle of a
rod-shaped bacterium? Chemical gradients are
key to directing this apparatus—in this case,
gradients of negative regulators of FtsZ help to
direct its assembly to the cell midpoint.
Specifically in E. coli, three proteins, designated MinC, MinD, and MinE, are the major
components of the FtsZ targeting system. MinC,
an inhibitor of FtsZ assembly, would simply
keep FtsZ rings from forming throughout the
cell without its two partners. One of them,
MinD, is an ATPase, while MinE stimulates that
ATPase activity.
Overall, according to current thinking,
MinD-ATP binds to the cytoplasmic membrane
via an amphipathic helix, but is dislodged from
Margolin a Changing Mix of Birds, Music, and the Cell Division Protein called FtsZ
William Margolin grew up in a
New Jersey suburb where newly
built houses sat on one-acre lots
with manicured front lawns and a
backdrop of woods— except for
his, where the woods inexplicably
were cut down. “My dad planted
some fruit trees in the back half, but
he got too busy to take care of
them,” Margolin recalls. “As a result, the back half became a wild
meadow when I was a few years
old, then a young forest. Because
this half-acre was kept natural—to
the disdain of the neighbors, no
doubt—I knew every tree, every
blackberry bush, and saw how they
fought for survival. I also got seriously involved in birds and bird
feeders. This propelled me on the
path to becoming a naturalist or
ecologist.”
However, Cornell University,
which had a strong ornithology
program, did not accept him when
he applied for undergraduate admission there more than 30 years
ago. Instead, he went to the Massachusetts Institute of Technology
(MIT), which offered no programs
in ornithology. “So, I was pushed
into more molecular directions
there,” he says. Like many biology
majors, he first saw himself on path
for a medical career, but soon discovered otherwise. After working
as a volunteer at a Boston hospital,
he says, “I realized rather quickly
that I did not feel comfortable with
hospitals or sick people, so that
nixed medicine for me.
“Fortunately, at the same time, I
was taking a very time-intensive lab
course in bacterial genetics with
Graham Walker, where the class
made random insertions of a lacZ
reporter in Escherichia coli to study
gene regulation,” he continues. “I
had not done research before, no
high school science projects or anything like that, so the fun of designing experiments and getting results
was eye-opening for me. It didn’t
hurt that Graham’s lab, as well as
MIT biology in general, had some
amazing scientists as role models,
which set the bar pretty high.”
Today Margolin, 48, is a professor in the department of microbiology and molecular genetics at the
University of Texas-Houston Medical School, where his primary research focus is on FtsZ, a protein
used in bacterial cell division. This
abundant protein, in response to
some unknown signal, polymerizes
into a ring structure marking the
cell division site, and is essential for
initiating cell division.
“I was fortunate to take my first
faculty position just when green
fluorescent protein was applied for
the first time as a tag to localize
proteins in living cells,” he says.
“Probably the most exciting time
for me was seeing many E. coli
bacteria swimming around under
the fluorescence microscope, each
one with its little glowing ring of
FtsZ. My lab today is focused on
understanding this machine that divides bacterial cells, mainly E. coli,
and the theme and variations of this
machine across the diverse spectrum of microbial species.
“The adventurous part of me
also undertook a project on understanding cell division in the archaea, but this has not yet borne
fruit, largely because of the inherent difficulties working with them.
My backyard roots are still there,
as I am a biologist first and foremost, and want to understand how
cells and organisms grow.”
After finishing his B.S. in biology
at MIT in 1981, he received his
Ph.D. in molecular biology in 1989
from the University of WisconsinMadison. He did research as a postdoctoral fellow in the department
of biological sciences at Stanford
University from 1989 to 1993. “I
remember asking Graham about
which graduate schools to apply to
for molecular genetics,” he says.
“Graham suggested that I go ask
David Botstein, who didn’t know
me personally, but he had taught
me undergraduate genetics, so I
knew him. It was like going to see
the Wizard—and I was the Cowardly Lion. But the Wizard appeared and spewed out: ‘Stanford,
Berkeley, Wisconsin,’ before dismissing me. I took this advice, and
ended up going to two out of the
three.”
Margolin grew up an only child
in Tenafly, N.J., the first scientist in
a long line of nonscientists—and
the first in his family to go to graduate school. In addition to nurturing his wild “backyard,” he further
indulged his love for ecology during long walks with his parents in
Greenbrook Sanctuary, a nature
preserve along the Palisades in New
Jersey, cliffs that overlook the Hudson River.
He met his wife, Sarah Slemmons, through a classical music
dating service while he was at Stanford. They have three daughters,
Sonia, 12, Sophie, 11, and Elena, 8.
His wife currently is a development
associate for the Houston Symphony. Margolin loves music. “I
spent a considerable amount of
time at the MIT music department,
possibly more time than in the biology department,” he says. “I almost did a music minor, as I had
composed a number of piano
pieces, and [composer/musician]
John Harbison was on the faculty.
Strangely, there was a room with a
grand piano next door to the improvised lab space for our bacterial
genetics course, and I would often
sneak in and play it.
“In an interesting parallel, there
is a piano in the art gallery here at
UT Medical School, and I used to
take breaks from looking under the
microscope by improvising on the
piano there,” he adds. “I don’t anymore, mainly because I’m too busy.”
Marlene Cimons
Marlene Cimons is a freelance writer
in Bethesda, Md.
Volume 3, Number 7, 2008 / Microbe Y 331
FIGURE 2
Assembly of the cell division machine at the membrane of E. coli. (A) With the help of the Min and nucleoid occlusion spatial regulators, FtsZ
(yellow boxes) assembles into protofilaments at the future division site. This assembly is dynamic, with FtsZ subunits undergoing constant
turnover. Other proteins such as FtsA may associate with FtsZ outside the ring. Interactions between FtsZ and FtsA (red), ZipA (purple), ZapA
(magenta) and other proteins help to tether the protofilaments to the inner surface of the cytoplasmic membrane and to promote lateral
interactions between protofilaments. (B) Once the FtsZ ring is in place, a number of transmembrane proteins are recruited. Some of these,
such as FtsB, FtsQ, FtsL, FtsI, and FtsN, span the membrane only once, while others, such as FtsK and FtsW, span the membrane multiple
times. (C) At the last stages of cytokinesis, the cell division machine has lost most of the FtsZ subunits, while many of the other proteins
may still persist in subcomplexes.
the membrane when MinE promotes ATP hydrolysis. MinD-ADP then diffuses in the cytoplasm until its ADP is exchanged for ATP, promoting a conformational change in MinD and
driving it to bind again to the membrane. When
MinE is at high concentrations, rebound MinDATP will not persist on the membrane because
the ATP will be hydrolyzed quickly. However,
when MinE concentrations drop, MinD-ATP
can remain bound to the membrane for tens of
seconds before local MinE levels increase sufficiently to dislodge it.
These dynamics cause MinD to migrate back
and forth from one cell pole to the other (Fig. 3),
with MinE lagging behind. This fluctuating process regulates cell division because MinC binds
efficiently to MinD, and thus goes along for the
ride, bringing MinC to the membrane near the
cell poles, where it can prevent assembly of FtsZ
rings there, but not at the cell center.
A cylindrical membrane carrying only the
three Min proteins has the asymmetry needed to
start oscillating, according to mathematical sim-
332 Y Microbe / Volume 3, Number 7, 2008
ulations. Moreover, because the time-averaged
MinC concentration is lowest at the cell center,
the FtsZ ring assembles there exclusively. When
my colleagues and I made the FtsZ protein fluorescent, we could see it migrating back and
forth en masse within the FtsZ spiral structure
of E. coli, but only in a min⫹ strain. It is likely
that FtsZ aggregates migrate in direct response
to the negative effects of migrating MinC.
If the Min system were the only spatial regulator of FtsZ rings, then, in its absence, we
would expect FtsZ rings to be randomly placed
in bacterial cells. However, in min- mutants,
FtsZ rings form at cell poles, producing minicells that lack chromosomal DNA, but do not
form on top of nucleoids. Instead, FtsZ rings
generally assemble only between separated
nucleoids, indicating that nucleoids themselves
have a negative regulatory role, called nucleoid
occlusion.
A few years ago, Ling Juan Wu and Jeff Errington from the University of Oxford, United
Kingdom, along with Thomas Bernhardt and
FIGURE 3
Dynamic assembly of the MinD protein helps to define the division plane. Shown is a time-lapse experiment with a field of E. coli cells
expressing gfp-minD, thus permitting direct visualization of periodic MinD protein localization by fluorescence microscopy. Fluorescence
images were captured at 15-second intervals. The last image was taken with differential interference contrast. Note the two separate MinD
oscillating systems already in place in the central dividing cell.
Piet de Boer at Case Western Reserve University
School of Medicine in Cleveland, Ohio, identified specific unrelated DNA-binding proteins
that regulate FtsZ assembly to mediate nucleoid
occlusion in B. subtilis and E. coli, respectively.
It remains to be seen how these proteins inhibit
FtsZ assembly only near nucleoids. Furthermore, in mutants lacking these proteins, FtsZ
rings still show a preference for assembling between nucleoids, indicating that other spatial
regulators are at work.
Variations on the Centering Theme
Many bacteria lack Min proteins, while others
such as B. subtilis contain MinC and MinD but
not MinE. However, their absence does not
prevent proper targeting of the FtsZ ring. In B.
subtilis, when MinE is absent, the MinCD complex no longer is chased from one cell pole to
the other. Instead, MinCD is held in place by
DivIVA, a protein that is conserved in many
gram-positive species and which localizes to cell
poles and division septa. Once anchored, MinC
forms a gradient, with a minimum at the cell
center prior to FtsZ ring formation, an outcome
similar to that of the migrating Min system of E.
coli.
Another variation on this theme is seen in
Caulobacter crescentus, according to Martin
Thanbichler and Lucy Shapiro of Stanford Uni-
versity, Stanford, Calif. In such cells, a single
protein, called MipZ, performs the roles of both
the Min system and nucleoid occlusion. MipZ,
an inhibitor of FtsZ assembly like MinC, binds
to the chromosomal origin of replication, called
oriC, which in a newly formed C. crescentus cell
is located at one cell pole. FtsZ forms a focus at
the opposite pole, presumably because it is the
farthest point from the MipZ inhibitor.
When this region of the chromosome is duplicated early in DNA replication, the new oriC is
rapidly moved to the other end of the cell, taking
bound MipZ with it. This locally high concentration of MipZ now dislodges the FtsZ focus.
Because MipZ is now concentrated near both
cell poles at the duplicated oriCs and is at its
lowest concentration at the cell midpoint, FtsZ
assembly is favored near the midpoint. Furthermore, the coupling of MipZ bipolar localization
to chromosome replication ensures that a central FtsZ ring will not form until the segregation
of the chromosome is under way (although,
unlike E. coli, C. crescentus has considerable
nucleoid density at the time and place of FtsZ
ring assembly).
Although many cocci lack Min homologs,
Neisseria species contain all three, leading one
to wonder how a migrating Min system sets up a
gradient of MinC that would define a specific
division plane in a sphere, then change the angle
of that plane 90° for the next division. Directly
Volume 3, Number 7, 2008 / Microbe Y 333
visualizing oscillating Min in Neisseria proves
difficult because such cells are so small.
However, in round mutants of E. coli, the
Min proteins of either E. coli or N. gonorrhoeae
migrate back and forth nearly exclusively along
the long axis of such cells. Because the long axis
of emerging daughter cells within diplococci is
orthogonal to that formed during the next division, the direction of Min protein oscillation
may be part of the mechanism for choosing the
next division plane. Perhaps other species of
rods or cocci that lack Min proteins have MipZlike mechanisms to specify division planes.
even though they grow at higher rates, resulting
in bigger cells.
Meanwhile, Mycobacterium tuberculosis
cells have FtsZ spirals but few rings while growing in macrophages, suggesting that the macrophage environment indirectly inhibits FtsZ ring
assembly, according to Ashwini Chauhan, Malini Rajagopalan, and coworkers at the University of Texas Health Center at Tyler. A number
of other FtsZ regulators have also been characterized, and many more will likely be discovered
because FtsZ plays a pivotal role in growth and
division.
Other Proteins Directly
Regulate FtsZ Assembly
Bacterial Actin Plays a Role
in FtsZ Ring Integrity
Whereas MinC, MipZ, and the nucleoid occlusion proteins are important spatial regulators of
FtsZ assembly that disassemble FtsZ polymers,
several other proteins also bind directly to FtsZ
and control its assembly. Some, such as SulA of
E. coli or YneA of B. subtilis, transiently inhibit
FtsZ assembly during the SOS response but have
no effect under nonstress conditions because
they are not being synthesized.
SulA is thought to act by sequestering FtsZ
monomers away from the assembled form. EzrA
is a B. subtilis membrane protein that localizes
to the FtsZ ring but also inhibits FtsZ assembly
throughout the cell, probably counteracting
positive assembly factors. ZipA is an E. coli
protein that shares the membrane topology of
EzrA and localizes to the FtsZ ring. However,
unlike EzrA, it promotes FtsZ assembly, most
likely by stimulating the bundling of protofilaments, and also helps to keep the FtsZ ring
anchored to the cytoplasmic membrane. ZapA,
which is conserved in gram-negative and grampositive species, is a soluble protein that
crosslinks FtsZ protofilaments and, like ZipA,
promotes bundling.
Growth rate and conditions also regulate
FtsZ assembly. UgtP is an enzyme in the glucolipid synthesis pathway of B. subtilis that
inhibits FtsZ assembly during growth in rich
medium, but not in poor medium. The decreased function of FtsZ in rich medium is the
basis by which cells in rich medium are larger
(longer) than those in poor medium, according
to Richard Weart, Petra Levin, and colleagues at
Washington University in St. Louis, Mo. The
former cells divide less frequently per unit mass
The actin homolog FtsA, like ZipA, has a special
relationship with FtsZ. For example, the ftsA
gene is often adjacent to the ftsZ gene, including
among species as divergent as E. coli and B.
subtilis. Like other FtsZ regulators, FtsA binds
directly to FtsZ. An amphipathic helix at the
carboxyl terminus of FtsA helps to anchor FtsZ
to the membrane, according to Sebastian Pichoff
and Joe Lutkenhaus of the University of Kansas
Medical Center in Kansas City.
Meanwhile, the essential function of ZipA,
which is not conserved outside the enterobacteria, can be replaced by an FtsA with a single
missense mutation, indicating that the two proteins have overlapping roles. This overlap implies that FtsA may also help to bundle FtsZ
protofilaments. In support of this idea, stronger
self-association of FtsA as dimers or oligomers
correlates with more robust FtsZ ring function.
Indeed, FtsA from Streptococcus pneumoniae
can form helical polymers in vitro, according to
Orietta Massidda of the University of Cagliari,
Italy, and coworkers. This behavior indicates
that its natural form in the cell may be a polymer
that simultaneously crosslinks FtsZ protofilaments and tethers them to membranes. Mutants
of FtsA that fail to dimerize efficiently do not
function in cell division and have dominant negative effects, destabilizing the FtsZ ring at the
same or lower concentrations of FtsA that normally promote integrity of the ring. Covalent
tethering of two dimerization-deficient subunits
of FtsA partially suppresses the defects, underscoring the positive effects of FtsA self-association on FtsZ ring integrity (Fig. 2).
It is not known whether dimerization or oli-
334 Y Microbe / Volume 3, Number 7, 2008
gomerization state of FtsA regulates FtsZ ring
dynamics, but this is an intriguing possibility
considering the important roles of various inhibitors and stimulators of FtsZ assembly in balancing overall FtsZ ring activity. For example, if
the balance is tipped too far in the direction of
disassembly, FtsZ rings fall apart before they
can constrict. On the other hand, if FtsZ assembly is too stable, FtsZ rings may not form properly from the FtsZ spiral, or existing rings may
not undergo the controlled disassembly that is
the likely force behind the final stages of cytokinesis.
Cell Division Depends on Protein
Interactions at the Membrane
Once the FtsZ ring is correctly targeted, assembled, and tethered to the membrane, it recruits a
number of transmembrane proteins (Fig. 2).
Several are essential for proper cytokinesis. For
example, the E. coli division machine first assembles FtsZ, ZipA, and FtsA, according to
Tanneke den Blaauwen of the University of Amsterdam in the Netherlands and coworkers. After a delay, this complex then recruits other
transmembrane proteins.
Although one of these late proteins, FtsI, is a
transpeptidase, and others such as FtsQ, FtsL,
and FtsB can form a subcomplex, little is known
about what role each of these proteins plays in
cytokinesis. Most of them are conserved across
diverse species, and in E. coli, inactivation of
just one freezes the ring complex and prevents
ring constriction. In addition, the Tol/Pal complex, which extends from the inner membrane to
the outer membrane, is a subcomplex of the E.
coli cell division machine, with an important
(though not essential) role in coordinating invagination of the outer membrane along with
the inner membrane and cell wall during cytokinesis, according to Matthew Gerding, Piet de
Boer, and collaborators at Case Western Reserve University School of Medicine.
How does such a large complex of proteins
assemble? Earlier, investigators thought that binary protein-protein interactions drive this process, basing this view on what appeared to be a
hierarchy in recruiting fluorescent proteins specified by cell division genes from a series of conditional mutants. Among them, FtsZ was the
first protein to be recruited, followed by FtsA/
ZipA, and then transmembrane proteins. If each
successive protein specifically interacted with
the previous protein in this pathway, it would
explain how the complex is assembled.
However, other evidence soon undermined
this model. For example, the later-assembling
transmembrane proteins fail to be recruited to
the FtsZ ring when either FtsA or ZipA is inactivated, implicating each as a vital link in the
chain of protein-protein interactions. Yet, an
altered FtsA bypasses the need for ZipA, and
recruitment of later proteins is normal. These
steps imply that ZipA recruits later proteins only
indirectly.
Along the same lines, when protein chimeras
are used, many later proteins can be recruited to
the FtsZ ring independently of some early proteins, according to Nathan Goehring and
Jonathan Beckwith at Harvard University Medical School in Boston, Mass. For example, a
protein in the middle of the recruitment pathway such as FtsQ could be targeted prematurely
to the FtsZ ring and it can recruit many of the
later proteins despite the absence of earlier ones
such as FtsA. Moreover, some proteins can be
recruited in reverse order, and some early proteins can interact directly with late ones.
Along with evidence from several two-hybrid
studies showing that some proteins in the complex have multiple interactions, these results
indicate that the cell division protein complex is
not formed by sequential contacts, but by a web
of protein-protein interactions that form subcomplexes. If the web is weakened, the machine
approaches the threshold of disassembly.
These findings suggest that the cell division
machine contains redundant components. Thus,
E. coli cells can withstand the loss of particular
components such as ZipA or FtsN so long as the
web can compensate. This overbuilding, however, complicates the task of defining the molecular role of each component.
Nevertheless, molecular genetics and structural biology are helping investigators to elucidate the role of individual protein domains in
forming the cell-division machinery. For example, the single transmembrane domain of FtsI is
sufficient for its recruitment to the FtsZ ring in
E. coli, according to Mark Wissel, David Weiss,
and coworkers at the University of Iowa, Iowa
City.
In B. subtilis cells, DivIB, a homolog of FtsQ,
contains three distinct epitopes, one in its transmembrane domain and two in its periplasmic
Volume 3, Number 7, 2008 / Microbe Y 335
domain, responsible for its recruitment to the
machine, according to Kimberly Wadsworth,
Glenn King, and collaborators at the University
of Queensland, Brisbane, Australia. Each of
these epitopes probably interacts with a different component of the machine, consistent with
the idea that DivIB is a central player in the web
of protein-protein interactions.
Conservation of FtsZ-Based
Fission Mechanisms
Once this machine fully assembles, the ring contracts and the cell division septum, cleavage
furrow, or a combination, depending on the
species, forms behind it. Although the mechanism for this process is not known, it might
depend on FtsZ pulling while it is tethered to the
membrane, the growing division septum in the
periplasm pushing on the collapsing ring, or a
combination of those two forces. Because some
bacteria divide without forming an obvious septum or cell wall, the former mechanism is potentially more universal.
Recent evidence supporting this possibility
comes from Masaki Osawa, Harold Erickson,
and coworkers at Duke University, who showed
that a purified FtsZ fused to a membrane targeting sequence could assemble into discrete rings
inside tubular liposomes; even more remarkably, the rings with the highest FtsZ concentrations could pinch the liposomes, although not to
completion. These findings suggest that FtsZ
polymers are sufficient to exert a contractile
force on the cytoplasmic membrane.
Data from sequenced genomes suggest that
the cytokinesis machinery is highly conserved.
For example, plant chloroplasts use multiple,
nuclear-encoded FtsZ molecules for chloroplast
fission, most likely of cyanobacterial provenance. Chloroplasts, like cyanobacteria, also
use the Min system to regulate placement of the
FtsZ ring. Chloroplast division also involves
multiple dividing rings. However, most other
bacterial cell division proteins do not seem to be
present in plants.
Protists such as Dictyostelium discoideum
harbor FtsZ homologs for mitochondrial fission. However, FtsZ is absent in fungi and animals, where another GTPase, dynamin, replaces
FtsZ in splitting organelles. Dictyostelium contains both dynamin and FtsZ.
Species of one of the major branches of the
archaea, the euryarchaea, have multiple FtsZ
orthologs that presumably orchestrate cytokinesis, although little is known about how they act.
In contrast, species belonging to the other major
branch, the crenarchaea, lack FtsZ or any other
recognizable bacterial cell division protein homolog. Even some bacteria lack FtsZ, notably
the Planctomyces-Verrucomicrobia-Chlamydia
branch. Some members of this diverse group of
bacteria contain tubulin homologs, although
their physiological roles are unknown.
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