REVIEWS
Septins: the fourth component of
the cytoskeleton
Serge Mostowy1,2,3,4 and Pascale Cossart1,2,3
Abstract | Septins belong to a family of proteins that is highly conserved in eukaryotes
and is increasingly recognized as a novel component of the cytoskeleton. All septins are
GTP-binding proteins that form hetero-oligomeric complexes and higher-order structures,
including filaments and rings. Recent studies have provided structural information about
the different levels of septin organization; however, the crucial structural determinants and
factors responsible for septin assembly remain unclear. Investigations on the molecular
functions of septins have highlighted their roles as scaffolds for protein recruitment and as
diffusion barriers for subcellular compartmentalization in numerous biological processes,
including cell division and host–microorganism interactions.
Institut Pasteur, Unité des
Interactions BactériesCellules, Département de
Biologie Cellulaire et
Infection, F-75015 Paris,
France.
2
Inserm, U604, F-75015
Paris, France.
3
INRA, USC2020,
F-75015 Paris, France.
4
Present address: Section
of Microbiology, Centre for
Molecular Microbiology and
Infection, Imperial College
London, Armstrong Road,
London SW7 2AZ, UK.
e-mails:
[email protected];
[email protected]
doi:10.1038/nrm3284
Published online
8 February 2012
1
Septins were first discovered 40 years ago in the budding yeast Saccharomyces cerevisiae using mutagenesi­s
screens pioneered by Lee Hartwell1 to find genes that
are crucial for cell division. These studies led to the
identification of four cell division cycle (CDC) genes
(cdc3, cdc10, cdc11 and cdc12), mutations in which
caused defects in cytokinesis. In parallel studies,
electro­n microscopy analysis of budding yeast identified filaments, ~10 nm thick, that encircled the neck
between mother and bud2. The protein products of
cdc3, cdc10, cdc11 and cdc12 were then shown by fluorescence microscopy to localize as rings to the septating
bud neck3,4, and they were thus named septins by John
Pringle. On the basis of this localization, and on data
showing that septin mutants lack bud neck filaments, it
was concluded that septins are the major component of
bud neck filaments during cell septation.
Since the discovery of septins in yeast, proteins with
homologous sequences have been identified in nearly
all eukaryotes, including humans 5–7. All septins are
GTP-binding proteins that control cellular processes
by polymerizing into hetero-oligomeric protein complexes that can further form filaments. Septins have
been recognized as cytoskeletal components because
of their filamentous appearance, as well as their association with cellular membranes, actin filaments and
microtubules. They not only assemble into filaments
and bundles but also may form rings, and they are thus
increasingly regarded as an unconventional component
of the cytoskeleton. However, unlike actin filaments and
microtubules, septin filaments are not polar, similarly to
intermediate filaments.
Despite growing interest in these cytoskeletal proteins, the molecular mechanisms of septin assembly
are much less understood than those of actin filaments,
microtubules and intermediate filaments (BOX 1). Solving
this issue has been difficult because of the multiple septins and septin isoforms and the different distribution
of septins in different cell types. Human septins purified
from Escherichia coli have been found to form hetero­
hexamers in vitro 8, but how septins function remains
mostly unknown. Their function is thought to depend
on interactions between several different septin­s and,
because of this complexity, different roles for different
septins have been observed, with some septin­s being
reported to be redundant. In agreement with this, the
knockout of certain septin genes in mice has failed to
produce phenotypes, whereas the knockout of other­s
is embryonic lethal (TABLE 1) (see Supplementary
informatio­n S1 (table)).
Several recent studies have provided structural
information on the different levels of septin organization (oligomeric complexes, filaments, bundles and
rings), clarifying the role of septin heterohexameric
complex formation in the assembly of higher-order
structures. At the same time, the expanding number of
functional studies has shown that septins orchestrate a
range of key cellular processes, including cytokinesis,
ciliogenesis and neurogenesis, by serving as scaffolds
for protein recruitment and/or as diffusion barriers to
compartmentalize discrete cellular domains. Studies of
host–microorganism interactions have also highlighted
unsuspected roles for septins during bacterial infection
and in innate immunity.
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Box 1 | The other cytoskeletal components
Actin
Actin is a ~40 kDa globular protein and is known as
globular actin (G‑actin) in its monomeric form. As an
ATPase, it hydrolyses ATP to ADP upon polymerization.
In microfilaments, long polymerized chains of actin are
intertwined in a helix, generating filaments (known as
filamentous actin (F-actin)) with a diameter of ~7 nm.
Actin filaments are polar, with a plus end (also known
as the barbed end), where monomers preferentially
assemble (see the figure), and a minus end (also known
as the pointed end), where monomers preferentially
disassemble.
Microtubules
Microtubules are cylindrical structures that are built
from 13 parallel protofilaments made of α‑tubulin and
β‑tubulin heterodimers. Each tubulin monomer of
~50 kDa binds one GTP molecule, and the α‑tubulin
GTP is locked in the interface between the α‑tubulin
and β‑tubulin; only the β‑tubulin GTP undergoes
hydrolysis. The tubulin dimers assemble in a
head-to-tail manner, producing microtubule polymers
with a diameter of ~25 nm. Similarly to actin,
microtubules are polar, with one end (the plus end)
growing faster than the other end (the minus end).
Microtubules can assemble and disassemble at the
plus end (see the figure), through a process known
as dynamic instability; disassembly is known as
catastrophe and rapid growth is known as rescue.
Actin
F-actin
G-actin
– End
+ End
Microtubules
Growing
α-tubulin
β-tubulin
– End
+ End
Shrinking
– End
+ End
Intermediate filaments
Filament
ULF
Tetramer
Intermediate filaments
Individual proteins assemble to form a tetrameric
subunit composed of two antiparallel half-staggered coiled-coil dimers. Next, eight
tetrameric
associate
Nature
Reviewssubunits
| Molecular
Cell Biology
laterally to form a unit length filament (ULF). Individual ULFs join end-to-end to form short filaments, and these grow into
longer filaments by longitudinally annealing to other ULFs and existing filaments (see the figure). Intermediate filaments
have a diameter of ~11 nm, and they are non-polar because of the antiparallel orientation of tetramers.
This Review focuses on these structural and functional advancements, which have greatly improved our
understanding of septin function in vivo, highlighting
how septin dysfunction may be linked to various diseases,
including cancer, neurological disorders and infections
(TABLE 1) (see Supplementary information S1 (table)).
Architecture of the septin cytoskeleton
The number of septin genes per organism is highly variable. For example, Caenorhabditis elegans has two septin
genes, S. cerevisiae has seven and humans have 13 (many
of which undergo alternative splicing)9. The encoded
13 septins in humans (SEPT1–SEPT12 and SEPT14;
SEPT13 is a pseudogene now called SEPT7P2) are either
ubiquitous or tissue specific, and they are classified,
based on sequence similarity, into four homology groups
named after their founding members10,11: SEPT2, SEPT3,
SEPT6 and SEPT7 (TABLE 1) (see Supplementary information S1 (table)). All four septin groups are represented
in vertebrates, but they do not have clear orthologous
relationships with the septins found in invertebrates5–7.
All septins can form heteromeric complexes, which
associate to form higher-order structures, including
filaments, rings and cage-like formations. These unique
structures are required to control cellular processes that
are localized, for example, at the division site12,13, the
plasma membrane14–16, the annuli of spermatozoa17,18,
the bases of cilia19–21 and dendrites22,23, and surrounding
invasive bacteria24,25.
Septin complex and filament formation. Septins are
small GTP-binding proteins of 30–65 kDa and belong
to the superclass of phosphate-binding loop (P‑loop)
NTPases, which includes the RAS-like GTP-binding
proteins26. All mammalian septins have a central core
domain (with a minimum sequence similarity of 70%),
which consists of a polybasic region that can bind
directly to phosphoinositides on the plasma membrane, a GTP-binding domain and 53 highly conserved
amino acids of unknown function called the septin
unique element (SUE)5,6 (FIG. 1a). Their amino- and
carboxy-termina­l regions contain Pro-rich and coiledcoil domains, respectively, which vary in length and
amino acid composition (within each septin group, the
C‑terminal regions share 50–60% sequence identity).
How these differences affect the functional properties
of septins is not known.
Unlike RAS-like GTP-binding proteins, septins
form hetero-oligomeric complexes. Understanding how
septin­s interact should thus provide insights into septin
function. When human SEPT2 lacking its C‑terminal
coiled-coil domain was expressed in E. coli, purified
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Table 1 | Classification of the human septins
Septin* Chromosomal
location
Expression
Functions
Disease association
Mouse knockout
phenotype
SEPT1
(SEPT2) 16p11.1 Lymphocytes and
cells of the CNS
ND Alzheimer’s disease,
cancer (colon, oral,
leukaemia, lymphoma)
ND
SEPT2
(SEPT2)
2q37.3
Ubiquitous Actin dynamics, bacterial autophagy,
cell shape and rigidity, chromosome
segregation, cilium formation,
cytokinesis, DNA repair, membrane
trafficking, microtubule regulation,
neurotransmitter release; acts as a
diffusion barrier at the base of the
cilium and as a scaffolding platform
Alzheimer’s disease, cancer
ND
(brain, liver, renal, leukaemia,
lymphoma), infection
(bacterial, viral), systemic
lupus erythematosus,
Von Hippel–Lindau syndrome
SEPT3
(SEPT3)
22q13.2
Cells of the CNS
ND Alzheimer’s disease,
cancer (brain), Down’s
syndrome, mesial temporal
lobe epilepsy
No CNS abnormalities
SEPT4
(SEPT2)
17q23
Lymphocytes and
cells of the CNS,
eyes and testes
Apoptosis, mechanical stability of
the annulus, membrane trafficking in
spermatozoa, mitchondrial function,
neurotoxicity; acts as a diffusion
barrier in spermatozoa
Alzheimer’s disease, cancer
(colon, skin, urogenital,
leukaemia), infection (viral),
male infertility, Parkinson’s
disease, schizophrenia
Asthenospermia,
enhancement of liver
fibrosis, enhancement of
neurotoxicity
by α‑synuclein,
hypodopaminergic
abnormalities, mild
cerebellar anomaly,
mitochondrial fission
defects
SEPT5
(SEPT2)
22q11.2
Ubiquitous
Axon growth, platelet biology
(secretion, ATP release), vesicle
targeting and exocytosis
Bipolar disorder, cancer
(pancreatic, leukaemia,
lymphoma), Parkinson’s
disease, schizophrenia
Increased platelet
sensitivity; no CNS
abnormalities
SEPT6
(SEPT6)
Xq24
Ubiquitous
Actin dynamics, cell shape,
microtubule regulation
Bipolar disorder, cancer
(skin, leukaemia, lymphoma),
Down’s syndrome,
infection (bacterial, viral)
schizophrenia
No additional effects
on MLL–‌Sept6-induced
leukaemia; no CNS or
systemic abnormalities,
even in double knockout
with Sept4
SEPT7
(SEPT7)
7p14.2
Ubiquitous
Actin dynamics, axon growth,
cell shape, chromosome segregation,
cytokinesis, dendrite formation,
DNA repair, membrane trafficking,
microtubule regulation, T cell motility;
acts as a scaffolding platform
Alzheimer’s disease,
cancer (nervous system),
Down’s syndrome, male
infertility
Embryonic lethal
SEPT8
(SEPT6) 5q31
Lymphocytes and
cells of the CNS,
eyes, intestinal
track and placenta
Neurotransmitter release
Retinal degeneration
ND
SEPT9
(SEPT3)
17q25
Ubiquitous
Actin dynamics, angiogenesis,
bacterial autophagy, cell motility,
cell proliferation, cell shape,
cytokinesis, microtubule regulation,
vesicle targeting and exocytosis
Cancer (breast, colon,
head, ovarian, neck,
leukaemia, lymphoma),
Down’s syndrome, hereditary
neuralgic amyotrophy,
infection (bacterial)
Embryonic lethal
SEPT10
(SEPT6)
2q13
Ubiquitous
ND
ND
ND
SEPT11
(SEPT6)
4q21
Ubiquitous
Actin dynamics, cell shape,
cytokinesis, dendrite formation,
membrane rigidity, membrane
trafficking, synaptic activity
Bipolar disorder,
cancer (renal, leukaemia,
lymphoma), schizophrenia
Embryonic lethal
SEPT12
(SEPT3)
16p13.3
Lymphocytes and
cells of the testes
Mechanical stability of the annulus
Male infertility
ND
SEPT14
(SEPT6)
7p11.2
Cells of the CNS
and testes
ND
Cancer (testicular)
ND
A fully referenced version of this table can be found in Supplementary information S1 (table). See also REFS 23,58. CNS, central nervous system;
ND, not determined. *Septin group is indicated in brackets.
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GTP binding
Pro-rich
Coiled-coil
SEPT2 group
N
C
SUE
Polybasic
SEPT3 group
N
N
*
N
b
SEPT7
GDP
SEPT6
C
SEPT6 group
C
SEPT7 group
C
SEPT2
SEPT2
GDP
GTP
SEPT6
GTP
GDP
SEPT7
GDP
~5 nm
a
~25 nm
Figure 1 | Septin complex and filament assembly. a | Schematic of prototypical
Nature Reviews | Molecular Cell Biology
septin structures. The 13 human septins (SEPT1–SEPT12
and SEPT14) are classified into
four groups (SEPT2, SEPT3, SEPT6 and SEPT7) based on sequence similarity. Human
septins consist of three conserved domains: a phosphoinositide-binding polybasic region,
a GTP-binding domain and the septin unique element (SUE); the length and sequence of
the amino-terminal and carboxy-terminal regions vary. Septins belonging to the SEPT6
group lack a Thr residue (Thr78), which prevents them from hydrolysing GTP to GDP
(indicated by an asterisk). b | The structure of the SEPT2–SEPT6–SEPT7 complex; two
copies of each septin are symmetrically arranged (SEPT7–SEPT6–SEPT2–SEPT2–SEPT6–
SEPT7) to generate a hexamer. Septin polybasic regions are indicated by arrowheads.
Arrows indicate the position and orientation of the coiled-coil domains, which are absent
from the crystal structure. Image in part b is modified, with permission, from REF. 8 ©
(2007) Macmillan Publishers Ltd. All rights reserved.
and co-crystallized with GDP, it formed a homodimer 8.
Although overexpression systems in mammalian cells
have also shown that SEPT2 can exist as a homodimer
(unlike overexpressed SEPT6 or SEPT9, which have
been suggested to exist only as monomers)14, endo­
genous septins seem to exist only as heterohexamers
or hetero-octamers27, and no physiological function for
septin homodimers has been assigned. Nevertheless,
the SEPT2 homodimer structure has been crucial in
building our understanding of septin–septin inter­
actions. On the basis of the obtained homodimer
structure, it was proposed that septins interact through
their GTP-binding domain (called the G interface)
and their N‑terminal and C‑terminal regions (called
the NC interface) (FIG. 2).This has since been confirmed
in structural studies examining yeast 28 and other
human8,29,30 septin–‌septi­n interactions.
By interacting as hetero-oligomers, septins can form
rod-shaped complexes28,31, which can then form filaments and other higher-order structures, such as rings.
Complexes contain two (C. elegans)31, three (human)8
or four (S. cerevisiae)28 different septins, each of which
is present in two copies, thereby generating tetrameric
(C. elegans), hexameric (human) and octameric complexes (S. cerevisiae). In all cases, the structure and the
order of septin monomers in the complex determine
the non-polarity of the filament; this is an important distinction from actin and microtubule filament structure
(BOX 1). Indeed, structural studies have provided insights
into how proteins are arranged within the complex.
Specifically, the structure of a complex of three human
septins (SEPT2, SEPT6 and SEPT7) has been solved
at a resolution of 4 Å (REF. 8). The structure was a nonpolar hexamer, ~25 nm in length and ~5 nm in diameter,
with two copies of each septin symmetrically arranged
(SEPT7–SEPT6–SEPT2–SEPT2–SEPT6–SEPT7)
(FIG. 1b). Strikingly, this hexameric complex showed
alternating G and NC interfaces within the complex —
that is, SEPT2 forms an NC interface with SEPT2 and a
G interface with SEPT6, and SEPT6 forms an G interface
with SEPT2 and a NC interfac­e with SEPT7.
Another well-characterized septin complex is that
of S. cerevisiae, in which two identical tetramers are
symmetrically arranged (Cdc11–Cdc12–Cdc3–Cdc10–
Cdc10–Cdc3–Cdc12–Cdc11)28. Similarly to the human
complex 8, the octameric yeast complex is non-polar.
Considering that the 13 septin genes in humans are
divided into four groups (TABLE 1), it is tempting to speculate that human septins may also form an octameric
complex. Indeed, recent work has shown that SEPT9 can
assemble onto either end of the SEPT7–SEPT6–SEPT2–
SEPT2–SEPT6–SEPT7 hexamer, thereby generating an
octamer 27,32,33. The precise arrangement of SEPT9 in
octameric complexes, and the relative contribution of
hexameric versus octameric complexes to higher-order
septin structures in humans, has yet to be defined.
Overall, septin filaments are probably assembled
from a mixture of hexamers and octamers; these all
include SEPT7 (which is ubiquitously expressed and
is the only member of the SEPT7 group) and variable
SEPT2, SEPT3 and SEPT6 group members arranged in
the complex according to cell type. As a result, mammalian septin complexes have a remarkable combinatorial
diversity that may be functionally important for roles
that cannot be carried out by other cytoskeleton components, in particular in highly specialized processes such
as ciliogenesis and neurogenesi­s (see below).
It is not yet known whether septins from the same
group can differentially affect higher-order structures and
septin function. At least in yeast, the deletion of specific
septins can result in the formation of alternative complexes and filaments, which are able to maintain septin
function34–37. Whether human septin complexes with distinct septin arrangements have distinct biochemical and
functional properties has yet to be shown. Nevertheless,
redundancy and interchangeability among septins most
probably diversify the repertoire of septin complexes, and
they have hampered functional studies for a long time.
Regulation of septin filament assembly. Structural studies
have addressed the role of nucleotide binding and hydrolysis in the regulation of septin–septin inter­actions8,28–30.
The different nucleotide states in septins may be important for the polymerization of septin filaments38 and the
dynamic structural transitions that are characteristic of
septin assemblies in vivo; however, this remains largely
speculative39,40. Strikingly, GTP hydrolysi­s can regulate septin–septin interactions by inducing conformational changes in the G and NC interaction interfaces,
which suggests that nucleotide-dependent changes in
structur­e enable or prevent septin–septin interactions8,29.
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CDC42
A RHO GTPase that regulates
numerous cellular functions,
including the cell cycle.
This situation is different from that of the classical small
GTPases, which cycle between an active GTP-bound state
and an inactive GDP-bound state to control complex cell­
ular processes41,42. Importantly, septins belonging to the
SEPT6 group lack a key Thr residue (Thr78), which prevents them from hydrolysing GTP to GDP29. As a result,
these septins are constitutively bound to GTP, and their
G and NC interaction interfaces cannot be regulated
by GTP hydrolysis. The inability of SEPT6 to hydrolyse
GTP suggests that GTP can stabilize the SEPT2–SEPT6
G interface without affecting the SEPT6–SEPT7 NC inter­
face, and this probably has a major role in septin complex
and filament formation.
When assembled end-to-end, septin complexes form
non-polar filaments8,28,31, which do not undergo dynamic
turnover as rapidly as actin filaments or microtubules16,43
and are thus regarded as more stable than other cytoskeletal elements. The ability to form filaments, as shown
in yeast36, is required for septin function and can occur in
response to specific triggers; for example, checkpoints
during cell division33,36 or signals during infection24,25.
Septin filaments can associate laterally, forming
bundled filaments, which can, in turn, assemble into
higher-order structures8,28,31,37,44 (FIG. 2); these filamentous
assemblies are considered to be the biologically active
form of septins. The lateral association of yeast septin
complexes is thought to be mediated by their C‑terminal
coiled-coil domains28, although evidence for this is so far
lacking for yeast septins in situ34,45 and for mammalian
septins8,46, in which the C‑terminal coiled-coil domains
may strictly function in filament assembly and stability.
The self-assembly of septin filaments in vivo is a reversible process47 and may be regulated by septin binding
partners. The first regulators of mammalian septin
organization to be identified were BORGs (binder­s of
RHO GTPases), a family of CDC42 effectors that can
directly bind SEPT6 or SEPT7 (REF. 48). As shown by
overexpression studies, the association of BORGs with
septins can markedly affect the distribution of septin
filaments within the cell.
Septins have been shown to interact with actin49,50
and microtubules14,51–55, as well as with phospholipid
membranes45,56, and these interactions can influence
septin assembly into filaments and rings. As a result,
understanding these interactions has helped to decipher
the mechanisms by which septins can assemble at specific locations in the cell. An actin-templated mode of
septin assembly has been shown49, and this is promoted
by the interaction of septins with actin-binding proteins. Indeed, septins have been shown in vitro to bind
the actin-binding protein anillin49, and anillin recruits
septins to the actomyosin ring during cell division57.
Moreover, septins have been shown in cells to bind nonmuscle myosin II25,50, and this interaction is thought to
promote the formation of septin filaments that associate with actin microfilaments in interphase cells and to
have a key role in cytokinesis50. As anillin is confined
to the nucleus during interphase49,50,57, it is likely that
non-muscle myosin II is crucial for the cytosolic regulation of septin–actin associations in non-dividing cells58,
for example in cell motility 59,60 or bacterial caging 25
G
NC
NC
G
G
NC
Subunits
Heterohexameric
complex
(rod-shaped)
Filaments
Bundled filaments
Ring
Nature Reviews
| Molecular
Cell Biology
Figure 2 | Septin cytoskeleton
dynamics.
Septin
subunits interact through their GTP-binding domain (called
the G interface) and amino‑terminal and carboxy‑terminal
regions (called the NC interface), forming complexes that
can join end-to-end to form filaments. Septins from
different groups are depicted in different colours. In
humans, septins (30–65 kDa) have been shown to form
complexes that contain three8 (or, as recently shown,
four27,32,33) septins, each of which is present in two copies,
and when complexes are assembled end-to-end they form
non-polar filaments. The resulting structure is a non-polar
heterohexamer (or a non-polar hetero-octamer when
complexes contain four septins from different groups; not
shown), with two copies of each septin symmetrically
arranged with alternating G and NC interfaces within the
complex. Septin filaments can associate laterally and form
bundles. Bundles of septin filaments can go on to form
higher-order structures, such as rings. Image is modified,
with permission, from REF. 128 © (2011) Elsevier.
(see below). Given the intimate relationship between
septins and actin dynamics described now for a range
of cellular processes, including filament formation49,61,
phagocytosis24,62 and bacterial actin-based motility 25, it is
tempting to speculate that septins may associate with the
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Actin-related protein 2/3
complex
(ARP2/3 complex).
A multiprotein complex
that consists of seven different
proteins and initiates new actin
filaments on pre-existing ones.
Sumoylation
A post-translational
modification involving the
addition of small ubiquitin-like
modifier (SUMO).
Ubiquitylation
The attachment of ubiquitin
to Lys residues of other
molecules, often as a
tag for their rapid cellular
degradation.
E3 ubiquitin ligase
A type of protein that is
classified according to the
presence of difference motifs,
such as HECT or RING
domains, and is involved
in the recognition and
ubiquitylation of a targeted
substrate for degradation.
Mitophagy
The autophagic turnover
of mitochondria.
Autophagy
A process in which cytosolic
constituents are sequestered
in a double-membraned vesicle
and delivered to the lysosome
for degradation.
Fluorescence recovery
after photobleaching
(FRAP). A microscopy
technique that is used to
measure the movement
(for example, diffusion rates) of
fluorescently tagged molecules
over time in vivo. Specific
regions in a cell are irreversibly
photobleached using a laser;
fluorescence is restored by
diffusion of fluorescently
tagged unbleached molecules
into the bleached area.
nucleating machinery of filamentous actin, for example
the actin-related protein 2/3 complex (ARP2/3 complex)
or Wiskott–Aldrich syndrome protein (WASP) family
protein­s, and thereby control actin polymerization. By
contrast, in the absence of actin polymerization, cytoplasmic septins change their organization from bundled filaments to rings, as shown by work using cyto­chalasin D,
an inhibitor of actin polymerization49.
In addition to associating with actin, septins colocalize with microtubules in numerous cell types61; however,
what mediates their interaction remains poorly understood. The GTP-binding domain of SEPT9 can interact
with microtubules52, but the role of GTP hydrolysis in
microtubule–septin binding remains to be determined.
Several studies have shown that microtubule-associated
septins filaments disassemble when cells are treated with
nocodazole, an inhibitor of microtubule polymerization,
suggesting a microtubule-templated mode of septi­n
assembly 14,51–53. In agreement with this, treatment of
cells with taxol, an inhibitor of microtubule disassembly,
increases the number of septin filaments53 and stabilizes
septin rings14.
Finally, septins have been found to interact with
phospholipids, and this interaction is also thought to
regulate septin filament assembly. Studies using purified
yeast septin complexes have shown that heter­o-octamer­s
polymerize into filaments on phosphatidylinositol‑4,5‑
bisphosphat­e (PtdIns4,5P2)-containing lipid mono­
layers45 that closely resemble the filamentous arrangements observed in situ 34. Moreover, work using
phospholipid-based liposomes and purified septin proteins has shown that mammalian septins can mediate
the tubulation of phospholipid membranes56. Strikingly,
interdependence exists between septin filament
assembl­y and the shape of phospholipid membranes:
phospho­lipids regulate the polymerization of septin
filaments, and septin filaments control the shape of the
phospho­lipid membrane. This membrane-facilitated
septin assembly is faster than the self-assembly of septin
filaments observed in vitro49, and it is probably central
to septin function in vivo.
Septin filament assembly and disassembly in vivo may
also be controlled by post-translational modifications,
including phosphorylation 37,63–66, sumoylation67,68 and
ubiquitylation69. Work in yeast has suggested that regulation of septin dynamics by phosphorylation is required
for the completion of cytokinesis63–66. As shown by mutation studies, protein kinases phosphorylate septin­s and
thereby help to promote their assembly at the bud neck.
Strikingly, phosphorylation of different septin amino
acid residues can determine the higher-order structure
of yeast septins, such as their assembly into rings or a
gauze-like meshwork37. Sumoylation also has a role in
regulating septin dynamics during the yeast cell cycle67,
and mutation of sumoylation sites in yeast septins results
in the accumulation of septin rings at the bud neck, suggesting that sumoylation is required for the disassembly
of septin rings. Interestingly, yeast two-hybrid screens
using human septins as ‘bait’ have recently identified
several non-septin interactors that are components
of the sumoylation and ubiquitylation machineries70.
In agreement with this, parkin, which is encoded by the
gene mutated in autosomal-recessive Parkinson’s disease71,
is an E3 ubiquitin ligase that is thought to mediate the degradation of SEPT5 (REF. 69). This suggests that ubiquitylation of septins may be necessary for their degradation.
As parkin activity is also crucial for mitophagy72, neuronal
dysfunction in Parkinson’s disease may result from the
accumulation of septins and/or their compartmentalized
proteins owing to defective autophagy (see below).
Molecular roles of septins
The septin field has entered a new era. Structural information at the different levels of septin assembly, showing how
septins form non-polar complexes and suggesting how
these complexes form unique shapes, has been helpfu­l
for understanding the molecular basis of septin function.
Below, we focus on the recently described roles of septins and discuss examples of them serving as scaffold­s for
protei­n recruitment or as diffusion barriers.
Septins as subcellular scaffolds. Higher-order septi­n
assemblies can act as scaffolds to accumulate proteins and promote their functional interaction. The
best-characterized example is from budding yeast, in
which, before cytokinesis, septins form a filamentous
hourglass-shaped structure that splits into two rings
(FIG. 3a). During the transition from hourglass shape to
rings, septin filaments rotate 90° from parallel to perpendicular along the mother bud neck44,73. Septin filaments are thought not to contribute to the generation
of contractile force47 but to participate in cytokinesis by
allowing several proteins that have important roles in
cytokinesis to accumulate at the division site (reviewed
in REFS 74–76). As in yeast, septins form a filamentous
hourglass structure at the division site in mammalian
cells and are required for the localization of many proteins (reviewed in REFS 12,13). Apart from the classic
septin scaffolds described for cytokinesis, there are now
several cases in mammalian cells of septin scaffolds
that function to maintain subcellular localization and
promot­e functiona­l protein–protein interactions47,58.
Septin assemblies have recently been shown to act as
scaffolds at the plasma membrane to regulate the distribution of membrane-bound proteins. (FIG. 3b). Using
atomic force microscopy (AFM), one study found that
inactivation of SEPT2 or SEPT11 reduced or increased,
respectively, the surface distribution of MET, and ligand–
receptor interactions were impaired in both cases.
Therefore, septins may control the distribution of surface
receptors and may also have a role in clathrin-mediated
endocytosis15,24,77,78. Similarly, studies using fluorescence
recovery after photobleaching (FRAP) have shown that
cortica­l septin assemblies can act as scaffolds and restrain
membrane-bound proteins with which they interact.
In this case, depletion of SEPT7 increased the turn­
over of the transmembrane protein glutamate aspartate
transporter (GLAST; which has been shown to directly
bind septins79), and administration of a septin filamentstabilizin­g drug, forchlorfenuron43, reduced it. The
cortical septin filaments could be mediating this by interacting with both the plasma membrane and actin15,16,58.
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a Cleavage furrow
b Plasma membrane
c Annulus
d Cilium
Daughter domain
Membrane
blebb
Cytokinetic
domain
Receptor
Transporter
Septin
ring
Daughter
domain
Septin
Cilium
Septin
ring
Anterior
Septin
ring
Posterior
Plasma
membrane
Figure 3 | Septins in several biological processes. Septins can act as scaffolds or diffusion barriers in several biological
Reviews
| Molecular
Cell Biology
processes in mammalian cells. a | Cytokinetic cells have two daughter domains and Nature
a cytokinetic
domain
at the cleavage
plane. Septin rings may form a diffusion barrier at the cleavage furrow and act as a scaffold for cytokinesis proteins.
b | Non-dividing cells have septin assemblies at the plasma membrane, which provide rigidity to the cell and act as a scaffold
to restrain membrane-bound proteins, including membrane receptors and transporters, and to retract the membrane
during blebbing. c | The annulus of the mammalian spermatozoon separates the anterior and posterior of the tail. A septin
ring forms a diffusion barrier at the annulus, where it is required for mechanical and structural integrity. d | To separate the
ciliary membrane from the plasma membrane, a septin ring forms a diffusion barrier at the base of the cilium, and this is
required for cilium formation. Images in parts a, c, d are modified, with permission, from REF. 92 © (2009) Elsevier.
Blebbing
The formation of an outward
bulge in the plasma membrane,
caused by localized disruption
of membrane–cytoskeleton
interactions. Blebbing is
important for several cellular
processes, including cell
motility.
Septin corset
Cortical septin filaments that
are oriented perpendicular to
the axis of travel. By providing
rigidity to the plasma
membrane, the septin corset
may help cells to maintain
direction during motility.
Exocyst
A eukaryotic protein complex
that is implicated in exocytosis.
Of note, cortical septins do not seem to form ring-like
structures in these cases. Interestingly, in other cases,
analysis using tagged septins has shown that septins can
assemble into rings at the plasma membrane14 and that this
depends on microtubules but not on filamentous actin.
Septins located at the plasma membrane, where
they may interact with phospholipids, cytoskeletal elements and/or other proteins, have been shown to confer
rigidit­y to the cell; indeed, depletion of SEPT2 or SEPT11
reduces cell stiffness and cortical elasticity, as measured
by AFM15. Septin-mediated plasma membrane rigidity
is important for regulating cell shape15,80 and for controlling the directional movement of cells20,59,60. Consistent
with this, the septin cytoskeleton has been linked to collective cell movement in Xenopus laevis embryos20, as
septi­n depletion induces plasma membrane blebbing during X. laevis gastrulation, which may affect the migration of cells20. Similarly, the depletion of SEPT7 impairs
the persistent motility of T cells and allows migration
through small pores59. Persistent motility is impaired
owing to the absence of a rigidifying septin corset59 and
the absence of septins to retract the membrane during
blebbing 60. Whether other T cell functions, such as T cell
receptor engagement at the immunological synapse81,
are compromised in the absence of septins has yet to be
determined. These two examples highlight the function
of septins during cell motility and may explain a role for
septins in cancer metastasis58, a process in which changes
in septin expression have been reported82,83.
Septin scaffolds may also regulate vesicle fusion
events84–89. SEPT5 has been shown to bind the mammalian exocyst complex and SNAREs (soluble NSF attachment protein receptors), which mediate vesicle docking
and fusion with the plasma membrane. Transfection of
cells with wild-type SEPT5 inhibits secretion, whereas
GTPase dominant-negative mutants show enhanced
secretion85. Overall, septin filaments seem to direct
the exocyst complex to the appropriate location at the
plasma membrane and to regulate the availability of
SNAREs for membrane fusion84–89.
Septin scaffolds can also assemble at specific intracytosolic locations. For example, septin filaments at
the mitotic midplane of epithelial cells help to localize
centromere-associated protein E (CENPE)90,91, a microtubule-dependent motor protein that is involved in
chromosome movement and spindle elongation. In the
absence of SEPT2 or SEPT7, chromosomes fail to align
properly and do not segregate. As a second exampl­e,
septi­n filaments have a key role in the spatial organization of the microtubule network53–55, and cells lacking
septins have fewer bundled and polyglutamylated microtubules and exhibit defects in vesicle transport 53,55. Thus,
septins can guide and modify microtubules and affect
motor-dependent transport. Considering the dynamic
ability of septin filaments to form in response to cell­
ular signals, it is likely that many more examples of
cytosolic septin scaffolds will emerge that may depend
on actin, microtubules and/or a source of membrane for
template­d assembly.
Septin-dependent diffusion barriers. Septin higherorder structures may also act as diffusion barriers
that compartmentalize membrane proteins to specific
cell­ular domains92. Such septin-dependent diffusion
barrier­s may isolate cellular appendages from the rest
of the cell. By forming ring-like structures at the base of
these appendages, septins prevent the diffusion of molecules in the membrane, although how septins precisely
contribute to this process remains to be determined92.
Septin-dependent compartmentalization was first
described in budding yeast, in which septin rings are
required to confine key membrane proteins at the
mother bud neck93,94. Experiments based on fluorescence loss in photobleaching (FLIP) and FRAP at the
yeast bud neck suggested the presence of diffusion barriers in the plasma membrane, the endoplasmic reticulum
(ER) and the nuclear envelope93–96. In septin-defective
cells, this compartmentalization was lost, indicating that
barrier establishment depends on septin function94–96.
Septin-dependent diffusion barrier formation may not
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Plasma membrane
a
Bacterium
b
Actin
Septin ring
c
d
Actin tail
f
Phagocytic
vacuole
g
h
e
Septin cage
i
Actin
Septin
Figure 4 | Cytoskeleton rearrangements during bacterial infection. a,b | Schematic
Reviews
| Molecular
Cell Biology
of different types of infection processes. InvasiveNature
bacteria
may enter
non-phagocytic
host cells through zippering (a) or triggering (b) mechanisms. In both cases, a cascade
of events leads to actin polymerization and cytoskeletal rearrangements, which allow
bacterial engulfment. Assembly of septin rings to the site of entry has been observed
and is thought to promote interaction with the plasma membrane. c | Bacteria are
subsequently internalized in a phagocytic vacuole. Some bacteria escape from the
phagocytic vacuole to the cytoplasm. d | Once released into the cytoplasm, bacteria may
form actin tails to move within the cell. Septins may form ring-like structures around
bacterial actin tails (not shown). e | In the case of Shigella flexneri, bacteria may be
trapped in septin cages, which are thought to restrict motility and therefore
dissemination. f | Recruitment of actin and septin (SEPT9) at the site of entry for
Listeria monocytogenes, a zippering bacterium. g | Recruitment of actin and septin
(SEPT9) at the site of entry for S. flexneri, a triggering bacterium. h | Recruitment of septin
(SEPT2) to the L. monocytogenes actin tail. i | Recruitment of septin (SEPT2) to cytosolic
S. flexneri devoid of actin tails; that is, the S. flexneri septin cage. Image in part g is
reproduced, with permission, from REF. 78 © (2009) Wiley-Liss. Image in part h is
reproduced, with permission, from REF. 25 © (2010) Elsevier.
Mitochondrial fission
A highly regulated process that
promotes fragmentation of the
mitochondrial network.
be required for cytokinesis per se97, but it is essential for
several processes that depend on the cellular segregation
of important components between mother and bud92,
such as ageing factors95. As in yeast, septins in mammals
probably also form a membrane diffusion barrier during
cytokinesis, although formal evidence for this has yet to
be obtained.
Interestingly, mammalian septins have been shown
to also form membrane diffusion barriers in nondividin­g cells (FIG. 3c). For example, in mammalian
sperm, membrane proteins are compartmentalized in
different regions of the sperm tail through a membraneassociate­d ring-like structure known as the annulus.
Septins are a major component of the annulus; as a
result, sperm from SEPT4‑knockout mice have no
annulus, and their spermatozoa lack membrane protein compartmentalization17,18. Male SEPT4‑knockout
mice are sterile because the morphology and motility
of their sperm flagella are defective, and the septinbased annulus is also defective in a subset of humans
with asthenospermia18. Thus, compartmentalization
of membrane by the septin cytoskeleton is critical for
the morphology and motility of mammalian spermatozoa. Unexpectedly, mitochondrial fission defects are
also observed in the absence of SEPT4 (REF. 17), suggesting that septins contribute to mitochondrial fission,
similarl­y to actin98.
Another example is cilia, which are antenna-like projections that sense extracellular signals through membrane protein receptors and transmit them into the cell
(for a review, see REF. 99) (FIG. 3d). A septin-dependent
diffusion barrier at the base of cilia has been proposed
to separate the ciliary membrane from the plasma membrane92. In line with this hypothesis, septins have been
shown to form ring-like structures at the base of motile
cilia of X. laevis embryos20 and primary cilia of mammalian cells19. In both X. laevis and mammalian cells,
decreasing septin expression impairs cilium formation. Moreover, studies using FRAP have shown that
decreasin­g septin expression enhances the diffusion
of membrane proteins at the base of cilia in mammalian cells19,20. In agreement with this, recent work has
described a ‘ciliopathy complex’ (a complex of nine proteins, seven of which are mutated in human patients with
ciliopathies), which functions to isolate the ciliary membrane from the rest of the cell and is restricted to the base
of the cilium by SEPT2 (REF. 21). Interestingly, SEPT2 is
also required for the maintenance of tubulin glutamylation55, a tubulin post-translational modificatio­n that is
directly linked to a human ciliopathy129.
Similarly to their role in cilia, septins form ring-like
structures at the bases of dendritic spines, which are
membranous protrusions of neurons that are involved
in relaying signals from neighbouring cells22,23. Depletion
of septins affects dendritic branch morphogenesis.
Although septins are presumed to compartmentalize the
dendrite membrane22,23, whether they control the diffusion of membrane proteins across the base of dendritic
spines remains to be demonstrated.
Functions of septins in infection
The study of host–microorganism interactions has
been instrumental in investigating the functions of
cytoskeletal components (reviewed in REFS 100–102).
This approach has recently been used to analyse septi­n
function and has revealed novel septin assemblies that
are formed during infection. Studies on bacterial invasion into the host cell and on bacterial actin-based
motility highlight a role for septin cage-like structures
in response to actin-dependent processes during host–
pathogen interactions (FIG. 4a–e). Consequently, septin
caging in bacterial infection can be used to investigate
the mechanisms and regulation of septin higher-order
assembly, and also offers new insights that may help to
combat infection.
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Septin roles in bacterial entry. Invasive bacteria have
evolved a range of mechanisms to exploit the host cell
actin cytoskeleton to enter cells100. They can invade
host cells through either zippering mechanisms (by
interacting with a host surface receptor) or triggering
mechanisms (by injecting proteins that that promote
cytoskeletal rearrangements) (FIG. 4a,b). In both cases,
a cascade of events leads to actin polymerization and
cytoskeletal rearrangements that are required for bacterial engulfment. Pathogen entry is controlled by many
factors, of either pathogen or host origin, and in most
cases the ARP2/3 complex is the main actin nucleator
that is usurped by bacteria to promote invasion100.
In contrast to the well-established role of actin during bacterial entry, septin function had not been investigated until recently. Studies focusing on the entry of
L. monocytogenes into epithelial cells have now revealed
a crucial role for these proteins24. Strikingly, septins surround invading bacteria and form ~0.6‑μm-wide collars (FIG. 4f,g), which are similar to the ring structures
observed in vitro using purified septin complexes49.
Interestingly, different septins seem to have distinct roles
during this process: SEPT2, and not SEPT11, is required
for septin assembly and recruitment to bacteria15,24,25,77.
This probably reflects different roles for SEPT2 and
SEPT6 group members in complex and ring formation
and is in accordance with AFM studies15. As a result,
decreasing the expression of SEPT2 reduces the entry of
L. monocytogenes 15,24, whereas decreasing the expression
of SEPT6 or SEPT11 enhances internalization of bacteria
into the host cell15,77. Whether GTP hydrolysis (and the
inability of SEPT6 group members to hydrolyse GTP29)
has a role in this process is unknown.
How septin rings are formed at the site of bacterial
entry remains to be determined. Insights into this issue
may come from the observation that septin collars are
formed next to the actin enrichment site24. When cells
are treated with cytochalasin D, septin recruitment is
impaired, indicating that actin polymerization precedes
septin assembly 24,62.
Actin tails
Columns of clustered,
branched actin fibres that
propel pathogens through the
cytosol of an infected cell.
Cytokine
A member of a large family of
secreted proteins that interact
with immune cells through
specific receptors. Cytokine
production results in the
activation of an intracellular
signalling cascade that
regulates immune function
and inflammation.
Septin recruitment to cytosolic bacteria. Some cytosolic
bacteria move within the cell using actin-based motility (reviewed in REFS 101,102). Most of the pathogens
studied so far form actin tails (FIG. 4d) by promoting actin
polymerization through the ARP2/3 complex, but different cytosolic bacteria have evolved different mechanisms
for doing so and also present different actin tail architectures101,102. It was recently shown that septins are recruited
to the actin tails of L. monocytogenes (which directly
activates ARP2/3 for actin tail polymerization using the
bacterial effector actin assembly-inducing (ActA)) and of
Shigella flexneri (which recruits neural WASP (N‑WASP)
and then ARP2/3 for actin tail polymerization through
the bacterial effector IcsA) in a process that is dependent on actin polymerization. Here, they form ring-like
structures that, unlike most of the other proteins that
are recruited to the actin tail, may surround the actin
tail and also the bacterial body 25 (FIG. 4h). The same has
been observed for all bacteria with actin tails tested
so far, which use different mechanisms to form actin
tails (including Listeria ivanovii, Rickettisa conorii and
Mycobacterium marinum)101 (S.M. and P.C., unpublished
observations). However, the role of septin rings at the
actin tail is currently unclear. Indeed, depletion of SEPT2
or SEPT9 from the host cell through RNA interference
did not affect the speed of movement of already motile
bacteria25. These data suggest that septin rings may have
a function other than regulating speed. This is consistent with earlier studies that had not identified septins as
essential for bacterial actin-based motility in vitro or in
cellular extracts103,104.
However, septin cage-like structures that may restrict
actin-based motility have been observed surrounding
cytosolic S. flexneri 25 (FIG. 4e,i). These structures require
actin polymerization, as treatment with cytochalasin D
inhibits their formation. Decreasing the expression of
SEPT2, SEPT9 or non-muscle myosin II inhibits septin
caging and increases the number of bacteria with actin
tails. Consistent with this, stimulation of septin caging by increasing SEPT2–non-muscle myosin II inter­
actions using tumour necrosis factor (TNF; a cytokine
that stimu­lates actomyosin contractility105) restricts actin
tail formation and cell-to-cell spread. Taken together,
these observations suggest that, in an infected host cell,
septins and non-muscle myosin II can be recruited
around actin-polymerizing bacteria to form cage-like
structures. Septin caging may serve to counteract actinbased motilit­y and restrict the dissemination of invasive pathogens, and it is therefore a novel mechanism of
host defence. The molecular and cellular events analysed
in vitro during bacterial infection now require validation
in vivo using relevant animal models. The consistency
with which S. flexneri can recruit septin cages (~20%
of bacteria are entrapped in septin cages during infection) and the stability of these structures as shown using
FRAP25 make the S. flexneri septin cage an attractive
model system to investigate fundamental mechanisms
of septin assembly, regulation and function.
Although septins are recruited to the L. monocyto­
genes actin tail, this bacterium is not compartmentalized by septin cages25,106. This indicates that septin caging
occurs in particular pathways of actin polymerization (in
this case, actin polymerization initiated by the recruitment of WASP family proteins, as occurs in S. flexneri
(see above)) and/or that additional factors, such as a
cytosolic source of membrane, are required to surround
the bacteria and facilitate septin assembly.
Interestingly, studies in Drosophila melanogaster
have identified ~0.6‑μm-wide cylindrical septin structures in the cytosol of non-dividing cells107,108. Just like
the S. flexneri septin cage25, these structures do not colocalize with anillin, nor do they require anillin to form.
However, they do require actin, as treatment with latrunculin A led to their disassembly 108. Therefore, septin caging may have other roles in addition to those within the
infection process.
Septins in bacterial autophagy. Cytosolic bacteria, such
as S. flexneri, can be targeted for autophagy after becoming compartmentalized in septin cages (see below for
L. monocytogenes). For this to occur, S. flexneri has to
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REVIEWS
be able to polymerize actin and recruit septin25,106,109,
as the S. flexneri IcsA mutant, which is unable to
polymerize actin and recruit septin, is not targeted for
autophagy. These results indicate that septin assembly
and autophagy may be interdependent. Similarly, when
SEPT2, SEPT9 or key autophagy components, such as
p62, nuclear dot protein 52 kDa (NDP52), autophagyrelated 5 (ATG5), ATG6 or ATG7, are depleted by RNA
interference, septin cages and autophagy markers fail to
accumulate around cytosolic S. flexneri 25,106. Autophagic
markers (for example, ubiquitin, p62 and ATG8) and
septin caging have also been observed around cytosolic
M. marinum25,106. This is probably because M. marinum
is similar to S. flexneri, in that it recruits WASP famil­y
proteins for actin tail polymerization 101. By contrast,
cytosolic L. monocytogenes expressing ActA (which
polymerizes actin through ActA and ARP2/3) is not
targeted for autophagy because ActA hides L. mono­
cytogenes from ubiquitylation and autophagic recognition25,106,110. As a result, ActA mutants are targeted for
autophagy independently of actin or septins.
Conclusions and perspectives
Septins are ubiquitous GTP-binding proteins that now
deserve recognition as the fourth cytoskeletal component.
Structural information about the different levels of septin
organization has recently fuelled valuable insights into the
molecular functions of septins. At the same time, studies
have highlighted the roles of septins as scaffolds for protein recruitment and as diffusion barriers for sub­cellular
compartmentalization. Remarkably, these functions are
not mutually exclusive and probably act in concert to
mediate septin-dependent processes.
However, many questions remain unanswered. How
septins function as a distinct component of the cytoskeleton remains to be fully determined, and solving this
issue will be a challenge. Moreover, the role of posttranslational modifications in mammalian septin assembly requires in-depth analysis. An important research
direction will be to systematically investigate the role of
post-translational modifications in mammalian septin
dynamics during cell division and other cellular processes. Considering the crucial role of septins 24,25 and
post-translational modifications111 in host–pathogen
interactions, bacterial infection may also be useful to
decipher the role of post-translational modifications in
the regulation of septin assembly and function.
The fact that septins form cage-like structures in
bacter­ial infection has provided a new molecular framework with which to understand septin assembly and
1.
2.
3.
Hartwell, L. H. Genetic control of the cell division cycle
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function. A major issue is now to decipher the mechanisms underlying septin recruitment at the site of actin
polymerization and during autophagosome formation.
Another aim is to determine the source of autophagosomal membrane112,130 in infection (plasma membrane113,
ER114 and/or mitochondria115).
The organization and precise function of septins
in autophagy promises to be important area of future
research. It may be that septin filaments affect the shape
of autophagic membranes, as shown for phospholipidbased liposomes in vitro56. Interestingly, autophagosome
biogenesis in both yeast and mammalian cells requires
homotypic fusion by SNAREs119,120, with which septins interact 85,86, and actin has been found to promote
the fusion of autophagosomes to lysosomes121. Septins
may therefore help to couple membrane acquisition
to autophagosome biogenesis and/or to regulate the
efficien­t fusion of autophagosomes to lysosomes.
Given the common machinery used for autophagy
from yeast to humans122,123, it is unlikely that the interdependence between septins and autophagy is limited
to bacterial autophagy. It will be crucial to investigate
the role of septin assemblies in various autophagic processes. The discovery of septin-mediated autophagy in
response to infection with intracellular pathogens25,106
may also uncover new ways in which autophagy can
function in immunity. Diseases that are characterized by defective autophagy include cancer, neuro­
degenerative diseases, ageing, autoimmune diseases
and inflammatory diseases124,125. As septin dysfunction
has been implicated in the pathogenesis of many of
these diseases58,82,126,127, one can speculate that defects in
autophagy underlie the pathogenesis of certain septin
disorders and vice versa.
Understanding the role of septin assemblies durin­g
infection by pathogens other than S. flexneri and
L. monocytogenes that recruit actin at distinct stages of
their infectious process, such as enteropathogenic E. coli
(EPEC)116 and Chlamydia trachomatis 117, may also help
in understanding septin-specific functions. Considering
that a group of septin-related genes, the paraseptins, are
found in bacteria26, it would also be interesting to study
their role in the bacterial cytoskeleton118.
Overall, the study of septins in infection has provided unsuspected insights into septin biology, and
septin recruitment by a range of pathogens will probably continue to highlight novel septin functions. This
may be helpful to decipher the molecular mechanisms
underlying human diseases in which septins have been
implicated (TABLE 1).
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Acknowledgements
Work in the Pascale Cossart laboratory is supported by the
Institut Pasteur, INSERM, INRA, Fondation Louis-Jeantet and
a European Research Council Advanced Grant Award
(233348).
Competing interests statement
The authors declare no competing financial interests.
FURTHER INFORMATION
Pascale Cossart’s homepage:
http://www.pasteur.fr/ip/easysite/pasteur/fr/recherche/
departements-scientifiques/biologie-cellulaire-et-infection/
unites-et-groupes/unite-des-interactions-bacteries-cellules
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