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The septin family of GTPases: architecture and dynamics

Nature Reviews Molecular Cell Biology volume 9, pages 478–489 (2008)Cite this article

Key Points

  • Septins comprise a conserved family of GTP-binding proteins that have multiple roles during cell division, cytoskeletal organization and membrane remodelling events.

  • Individual septins form smaller core complexes both in vivo and in vitro and contain, depending on the organism, two, three or four septins, each present in two copies. Core complexes oligomerize to form higher-order structures in vivo.

  • Electron microscopy and crystallographic studies have revealed that the septin core structure is mediated by interactions between GTP-binding domains across two distinct dimerization interfaces. Metazoan core complexes, in which the core complex architecture has been determined, oligomerize to form filaments across G-dimer interfaces, whereas the Saccharomyces cerevisiae complex forms complexes across the NC-dimer interface.

  • The G-dimer interface of septin oligomers is similar to the dimerization interface that is observed for the related Toc GTPases, which suggests that mechanistic similarities may exist between these evolutionarily related GTPases. However, the functional consequences of GTP binding and hydrolysis by septins for complex formation remain mysterious.

  • Septin core complexes form higher-order filaments that can dynamically engage the plasma membrane at the bud neck in S. cerevisiae, undergoing complex topological transitions during the cell cycle.

  • It remains unclear how septin-filament assembly is regulated and precisely how GTP binding and hydrolysis, as well as protein cofactors, regulate the assembly and disassembly of septin structure in vivo.

Abstract

Septins comprise a conserved family of proteins that are found primarily in fungi and animals. These GTP-binding proteins have several roles during cell division, cytoskeletal organization and membrane-remodelling events. One factor that is crucial for their functions is the ordered assembly of individual septins into oligomeric core complexes that, in turn, form higher-order structures such as filaments, rings and gauzes. The molecular details of these interactions and the mechanism by which septin-complex assembly is regulated have remained elusive. Recently, the first detailed structural views of the septin core have emerged, and these, along with studies of septin dynamics in vivo, have provided new insight into septin-complex assembly and septin function in vivo.

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Figure 1: Domain structure and classification of septins.
Figure 2: Core septin complexes share a common geometry.
Figure 3: Structure of the septin monomer and filament.
Figure 4: Structural similarities between septins and the Toc family of paraseptins.
Figure 5: Model for septin dynamics at the bud neck.

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Acknowledgements

We thank E. Nogales, J. Thorner, M. A. McMurray and colleagues for sharing data before publication and for critical reading of the manuscript. We thank T. L. Weirich for help in computer modelling of septin filaments. We also thank members of the Barral laboratory for discussion. J.P.E. is an European Molecular Biology Organization (EMBO) fellow. C.S.W. is a Human Frontier Science Program (HFSP) fellow.

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Authors and Affiliations

  1. Institute of Biochemistry, ETH Zürich, Zürich, 8093, Switzerland

    Christine S. Weirich & Yves Barral

  2. Institute of Molecular Biology and Biophysics, ETH Zürich, Zürich, 8093, Switzerland

    Jan P. Erzberger

Authors
  1. Christine S. Weirich
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  2. Jan P. Erzberger
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  3. Yves Barral
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Corresponding author

Correspondence to Yves Barral.

Supplementary information

41580_2008_BFnrm2407_MOESM1_ESM.pdf

Supplementary information S1 (figure) | Structure-guided sequence alignment of the G-domains of human SEPT2, SEPT6, SEPT7, Arabidopsis thaliana Toc33 and Pisum sativum Toc34. (PDF 1374 kb)

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DATABASES

Protein Data Bank

1ctq

1h65

2qa5

2qag

1wq1

FURTHER INFORMATION

Yves Barral's homepage

Jan Erzberger's homepage

Glossary

Cytokinesis

The process of cytoplasmic division.

Coiled-coil domain

A structural motif in proteins that consists of two or more α-helices that twist around each other, similar to a rope, to form a stable, rod-like structure.

Anaphase

The phase during eukaryotic mitosis during which chromosomes are segregated.

Hyphal growth

A type of vegetative growth in fungi in which cells are divided by incomplete septa, allowing transfer of cytoplasm and sometimes of larger structures, such as ribosomes, mitochondria and nuclei, between cells.

Pseudohyphal growth

A type of fungal vegetative growth during which hyphal-like structures are formed. During pseudohyphal growth, cells do not share cytoplasm.

Cleavage furrow

A constriction or indentation of the plasma membrane that marks the beginning of cytokinesis in animal cells.

Spindle midbody

The remnant of the spindle midzone and cleavage furrow in animal cells. The spindle midbody contains proteins and occupies the narrow channel that connects daughter cells upon completion of cytokinesis.

Cellularization membrane

The region of the plasma membrane that encloses nuclei and surrounding cytoplasm to form the cellular blastoderm in Drosophila melanogaster eggs, which contain approximately 5,000 nuclei within a shared cytoplasm.

P-loop

(Phosphate-binding loop). A nucleotide-binding-site motif that is found in many ATPases and GTPases.

Polarized fluorescence microscopy

An optical technique in which polarized light is used to excite a fluorophore. Because excitation depends on the direction of the dipole relative to the polarized light, this method can be used to determine the orientation of a population of fluorophores, provided that they are rigidly and uniformly orientated.

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 of a cell are irreversibly photobleached using a laser; fluorescence is restored by diffusion of fluorescently tagged unbleached molecules into the bleached area.

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Weirich, C., Erzberger, J. & Barral, Y. The septin family of GTPases: architecture and dynamics. Nat Rev Mol Cell Biol 9, 478–489 (2008). https://doi.org/10.1038/nrm2407

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