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Septins: the fourth component of the cytoskeleton

Key Points

  • Septins belong to a family of GTP-binding proteins that is highly conserved in eukaryotes and is recognized as a novel component of the cytoskeleton. They assemble to form hetero-oligomeric complexes, filaments, bundles and rings.

  • How septins assemble for function, and how they interact and work in conjunction with actin, microtubules and phospholipids, is the focus of intense investigation.

  • Septins have recently been reported to act as scaffolds for protein recruitment at the plasma membrane and in the cytosol, and as diffusion barriers for subcellular compartmentalization at the bases of cilia, at the annuli of spermatozoa and at the bases of dendritic spines in neurons.

  • Studies of host–microorganism interactions have highlighted roles for septins in bacterial invasion and autophagy.

  • Septin biology will help to decipher the molecular mechanisms underlying human diseases in which septins have been implicated, such as cancer, neurological disorders and infections.

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.

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Figure 1: Septin complex and filament assembly.
Figure 2: Septin cytoskeleton dynamics.
Figure 3: Septins in several biological processes.
Figure 4: Cytoskeleton rearrangements during bacterial infection.

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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).

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Correspondence to Serge Mostowy or Pascale Cossart.

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Glossary

CDC42

A RHO GTPase that regulates numerous cellular functions, including the cell cycle.

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.

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.

Mitochondrial fission

A highly regulated process that promotes fragmentation of the mitochondrial network.

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.

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Mostowy, S., Cossart, P. Septins: the fourth component of the cytoskeleton. Nat Rev Mol Cell Biol 13, 183–194 (2012). https://doi.org/10.1038/nrm3284

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