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Septins: the fourth component of the cytoskeleton

Nature Reviews Molecular Cell Biology volume 13, pages 183–194 (2012)Cite this article

Subjects

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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References

  1. Hartwell, L. H. Genetic control of the cell division cycle in yeast: IV. Genes controlling bud emergence and cytokinesis. Exp. Cell Res. 69, 265–276 (1971).

    Article  CAS  PubMed  Google Scholar 

  2. Byers, B. & Goetsch, L. A highly ordered ring of membrane-associated filaments in budding yeast. J. Cell Biol. 69, 717–721 (1976).

    Article  CAS  PubMed  Google Scholar 

  3. Haarer, B. K. & Pringle, J. R. Immunofluorescence localization of the Saccharomyces cerevisiae CDC12 gene product to the vicinity of the 10nm filaments in the mother-bud neck. Mol. Cell. Biol. 7, 3678–3687 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Kim, H. B., Haarer, B. K. & Pringle, J. R. Cellular morphogenesis in the Saccharomyces cerevisiae cell cycle: localization of the CDC3 gene product and the timing of events at the budding site. J. Cell Biol. 112, 535–544 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. Cao, L. et al. Phylogenetic and evolutionary analysis of the septin protein family in metazoan. FEBS Lett. 581, 5526–5532 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Pan, F., Malmberg, R. & Momany, M. Analysis of septins across kingdoms reveals orthology and new motifs. BMC Evol. Biol. 7, 103 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nishihama, R., Onishi, M. & Pringle, J. R. New insights into the phylogenetic distribution and evolutionary origins of the septins. Biol. Chem. 392, 681–687 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sirajuddin, M. et al. Structural insight into filament formation by mammalian septins. Nature 449, 311–315 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Russell, S. E. H. & Hall, P. A. Septin genomics: a road less travelled. Biol. Chem. 392, 763–767 (2011).

    Article  CAS  PubMed  Google Scholar 

  10. Kinoshita, M. The septins. Genome Biol. 4, 236 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Weirich, C. S., Erzberger, J. P. & Barral, Y. The septin family of GTPases: architecture and dynamics. Nature Rev. Mol. Cell Biol. 9, 478–489 (2008).

    Article  CAS  Google Scholar 

  12. Kinoshita, M. & Noda, M. Roles of septins in the mammalian cytokinesis machinery. Cell Struct. Funct. 26, 667–670 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Joo, E., Tsang, C. W. & Trimble, W. S. Septins: traffic control at the cytokinesis intersection. Traffic 6, 626–634 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Sellin, M. E., Holmfeldt, P., Stenmark, S. & Gullberg, M. Microtubules support a disc-like septin arrangement at the plasma membrane of mammalian cells. Mol. Biol. Cell 22, 4588–4601 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mostowy, S. et al. A role for septins in the interaction between the Listeria monocytogenes invasion protein InlB and the Met receptor. Biophys. J. 100, 1949–1959 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hagiwara, A. et al. Submembranous septins as relatively stable components of actin-based membrane skeleton. Cytoskeleton 68, 512–525 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Kissel, H. et al. The Sept4 septin locus is required for sperm terminal differentiation in mice. Dev. Cell 8, 353–364 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Ihara, M. et al. Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa. Dev. Cell 8, 343–352 (2005). References 17 and 18 report the generation of SEPT4-knockout mice and show the crucial role of septin diffusion barriers in mammalian spermatozoa.

    Article  CAS  PubMed  Google Scholar 

  19. Hu, Q. et al. A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science 329, 436–439 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kim, S. K. et al. Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. Science 329, 1337–1340 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chih, B. et al. A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain. Nature Cell Biol. 14, 61–72 (2011). References 19–21 are the first reports of septin diffusion barriers at the bases of mammalian and X. laevis cilia, suggesting that septin dysfunction may be a molecular determinant underlying human ciliopathies.

    Article  PubMed  CAS  Google Scholar 

  22. Tada, T. et al. Role of septin cytoskeleton in spine morphogenesis and dendrite development in neurons. Curr. Biol. 17, 1752–1758 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Xie, Y. et al. The GTP-binding protein septin 7 is critical for dendrite branching and dendritic-spine morphology. Curr. Biol. 17, 1746–1751 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. Mostowy, S. et al. Septins regulate bacterial entry into host cells. PLoS ONE 4, e4196 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Mostowy, S. et al. Entrapment of intracytosolic bacteria by septin cage-like structures. Cell Host Microbe 18, 433–444 (2010). Describes the discovery of a novel mechanism of host defence against intracytosolic bacteria, the septin cage, and provides the first link between septins and autophagy.

    Article  CAS  Google Scholar 

  26. Leipe, D. D., Wolf, Y. I., Koonin, E. V. & Aravind, L. Classification and evolution of P-loop GTPases and related ATPases. J. Mol. Biol. 317, 41–72 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Sellin, M. E., Sandblad, L., Stenmark, S. & Gullberg, M. Deciphering the rules governing assembly order of mammalian septin complexes. Mol. Biol. Cell 22, 3152–3164 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bertin, A. et al. Saccharomyces cerevisiae septins: supramolecular organization of heterooligomers and the mechanism of filament assembly. Proc. Natl Acad. Sci. USA 105, 8274–8279 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sirajuddin, M., Farkasovsky, M., Zent, E. & Wittinghofer, A. GTP-induced conformational changes in septins and implications for function. Proc. Natl Acad. Sci. USA 106, 16592–16597 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zent, E., Vetter, I. & Wittinghofer, A. Structural and biochemical properties of Sept7, a unique septin required for filament formation. Biol. Chem. 392, 791–797 (2011).

    Article  CAS  PubMed  Google Scholar 

  31. John, C. M. et al. The Caenorhabditis elegans septin complex is nonpolar. EMBO J. 26, 3296–3307 (2007). References 8, 28 and 31 are the first reports on the crystal structures of human, C. elegans and yeast septin complexes. They illuminate how septins form hetero-oligomeric complexes and non-polar filaments.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sandrock, K. et al. Characterization of human septin interactions. Biol. Chem. 392, 751–761 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. Kim, M. S., Froese, C. D., Estey, M. P. & Trimble, W. S. SEPT9 occupies the terminal positions in septin octamers and mediates polymerization-dependent functions in abscission. J. Cell Biol. 195, 815–826 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bertin, A. et al. Three-dimensional ultrastructure of the septin filament network in Saccharomyces cerevisiae. Mol. Biol. Cell 7 Dec 2011 (doi:10.1091/mbc.E11-10-0850).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. McMurray, M. A. & Thorner, J. Septin stability and recycling during dynamic structural transitions in cell division and development. Curr. Biol. 18, 1203–1208 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. McMurray, M. A. et al. Septin filament formation is essential in budding yeast. Dev. Cell 20, 540–549 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Garcia, G. et al. Subunit-dependent modulation of septin assembly: budding yeast septin Shs1 promotes ring and gauze formation. J. Cell Biol. 195, 993–1004 (2011). Reports the phosphorylation of different septin amino acid residues and the striking impact that these have on the higher-order structure of yeast septins.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mendoza, M., Hyman, A. A. & Glotzer, M. GTP binding induces filament assembly of a recombinant septin. Curr. Biol. 12, 1858–1863 (2002).

    Article  CAS  PubMed  Google Scholar 

  39. Vrabioiu, A. M., Gerber, S. A., Gygi, S. P., Field, C. M. & Mitchison, T. J. The majority of the Saccharomyces cerevisiae septin complexes do not exchange guanine nucleotides. J. Biol. Chem. 279, 3111–3118 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Mitchison, T. J. & Field, C. M. Cytoskeleton: what does GTP do for septins? Curr. Biol. 12, R788–R790 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Vetter, I. R. & Wittinghofer, A. The guanine nucleotide-binding switch in three dimensions. Science 294, 1299–1304 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Wittinghofer, A. & Vetter, I. R. Structure–function relationships of the G domain, a canonical switch motif. Annu. Rev. Biochem. 80, 943–971 (2011).

    Article  CAS  PubMed  Google Scholar 

  43. Hu, Q., Nelson, W. J. & Spiliotis, E. T. Forchlorfenuron alters mammalian septin assembly, organization, and dynamics. J. Biol. Chem. 283, 29563–29571 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. DeMay, B. S. et al. Septin filaments exhibit a dynamic, paired organization that is conserved from yeast to mammals. J. Cell Biol. 193, 1065–1081 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bertin, A. et al. Phosphatidylinositol-4,5-bisphosphate promotes budding yeast septin filament assembly and organization. J. Mol. Biol. 404, 711–731 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. de Almeida Marques, I. et al. Septin C-terminal domain interactions: implications for filament stability and assembly. Cell Biochem. Biophys. 15 Oct 2011 (doi:10.1007/s12013-011-9307-0).

    Article  CAS  Google Scholar 

  47. Kinoshita, M. Diversity of septin scaffolds. Curr. Opin. Cell Biol. 18, 54–60 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Joberty, G. et al. Borg proteins control septin organization and are negatively regulated by Cdc42. Nature Cell Biol. 3, 861–866 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Kinoshita, M., Field, C. M., Coughlin, M. L., Straight, A. F. & Mitchison, T. J. Self- and actin-templated assembly of mammalian septins. Dev. Cell 3, 791–802 (2002). Shows how septin–actin interactions can influence septin assembly into filaments and rings.

    Article  CAS  PubMed  Google Scholar 

  50. Joo, E., Surka, M. C. & Trimble, W. S. Mammalian SEPT2 is required for scaffolding nonmuscle myosin II and its kinases. Dev. Cell 13, 677–690 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Surka, M. C., Tsang, C. W. & Trimble, W. S. The mammalian septin MSF localizes with microtubules and is required for completion of cytokinesis. Mol. Biol. Cell 13, 3532–3545 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Nagata, K. et al. Filament formation of MSF-A, a mammalian septin, in human mammary epithelial cells depends on interactions with microtubules. J. Biol. Chem. 278, 18538–18543 (2003).

    Article  CAS  PubMed  Google Scholar 

  53. Bowen, J. R., Hwang, D., Bai, X., Roy, D. & Spiliotis, E. T. Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia. J. Cell Biol. 194, 187–197 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kremer, B. E., Haystead, T. & Macara, I. G. Mammalian septins regulate microtubule stability through interaction with the microtubule-binding protein MAP4. Mol. Biol. Cell 16, 4648–4659 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Spiliotis, E. T., Hunt, S. J., Hu, Q., Kinoshita, M. & Nelson, W. J. Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules. J. Cell Biol. 180, 295–303 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tanaka-Takiguchi, Y., Kinoshita, M. & Takiguchi, K. Septin-mediated uniform bracing of phospholipid membranes. Curr. Biol. 19, 140–145 (2009). Makes an important step in understanding the mechanisms underlying septin assembly, highlighting interdependence between septin assembly and membrane curvature.

    Article  CAS  PubMed  Google Scholar 

  57. Oegema, K., Savoian, M. S., Mitchison, T. J. & Field, C. M. Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis. J. Cell Biol. 150, 539–552 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Saarikangas, J. & Barral, Y. The emerging functions of septins in metazoans. EMBO Rep. 12, 1118–1126 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Tooley, A. J. et al. Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility. Nature Cell Biol. 11, 17–26 (2009).

    Article  CAS  PubMed  Google Scholar 

  60. Gilden, J., Peck, S., Chen, Y. C. & Krummel, M. F. The septin cytoskeleton facilitates membrane retraction during motility and blebbing. J. Cell Biol. 196, 103–114 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Spiliotis, E. T. & Nelson, W. J. in The Septins (eds Hall, P. A., Russell, S. E. H. & Pringle, J. R.) 229–246 (Wiley-Blackwell, 2008).

    Book  Google Scholar 

  62. Huang, Y. W. et al. Mammalian septins are required for phagosome formation. Mol. Biol. Cell 19, 1717–1726 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Dobbelaere, J., Gentry, M. S., Hallberg, R. L. & Barral, Y. Phosphorylation-dependent regulation of septin dynamics during the cell cycle. Dev. Cell 4, 345–357 (2003).

    Article  CAS  PubMed  Google Scholar 

  64. Barral, Y., Parra, M., Bidlingmaier, S. & Snyder, M. Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast. Genes Dev. 13, 176–187 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mortensen, E. M., McDonald, H., Yates, J. & Kellogg, D. R. Cell cycle-dependent assembly of a Gin4-septin complex. Mol. Biol. Cell 13, 2091–2105 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Versele, M. & Thorner, J. Septin collar formation in budding yeast requires GTP binding and direct phosphorylation by the PAK, Cla4. J. Cell Biol. 164, 701–715 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Johnson, E. S. & Blobel, G. Cell cycle regulated attachment of the ubiquitin-related protein SUMO to the yeast septins. J. Cell Biol. 147, 981–994 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Johnson, E. S. & Gupta, A. A. An E3-like factor that promotes SUMO conjugation to the yeast septins. Cell 106, 735–744 (2001).

    Article  CAS  PubMed  Google Scholar 

  69. Zhang, Y. et al. Parkin functions as an E2-dependent ubiquitin protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc. Natl Acad. Sci. USA 97, 13354–13359 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Nakahira, M. et al. A draft of the human septin interactome. PLoS ONE 5, e13799 (2011).

    Article  CAS  Google Scholar 

  71. Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605–608 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Youle, R. J. & Narendra, D. P. Mechanisms of mitophagy. Nature Rev. Mol. Cell Biol. 12, 9–14 (2011).

    Article  CAS  Google Scholar 

  73. Vrabioiu, A. M. & Mitchison, T. J. Structural insights into yeast septin organization from polarized fluorescence microscopy. Nature 443, 466–469 (2006).

    Article  CAS  PubMed  Google Scholar 

  74. Gladfelter, A. S., Pringle, J. R. & Lew, D. J. The septin cortex at the yeast mother-bud neck. Curr. Opin. Microbiol. 4, 681–689 (2001).

    Article  CAS  PubMed  Google Scholar 

  75. McMurray, M. & Thorner, J. Septins: molecular partitioning and the generation of cellular asymmetry. Cell Div. 4, 18 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Versele, M. & Thorner, J. Some assembly required: yeast septins provide the instruction manual. Trends Cell Biol. 15, 414–424 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Mostowy, S. et al. Septin 11 restricts InlB-mediated invasion by Listeria. J. Biol. Chem. 284, 11613–11621 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mostowy, S. & Cossart, P. Cytoskeleton rearrangements during Listeria infection: clathrin and septins as new players in the game. Cell. Motil. Cytoskel. 66, 816–823 (2009).

    Article  CAS  Google Scholar 

  79. Kinoshita, N. et al. Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astrocytes. Genes Cells 9, 1–14 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Kremer, B. E., Adang, L. A. & Macara, I. G. Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Cell 130, 837–850 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Billadeau, D. D., Nolz, J. C. & Gomez, T. S. Regulation of T-cell activation by the cytoskeleton. Nature Rev. Immunol. 7, 131–143 (2007).

    Article  CAS  Google Scholar 

  82. Peterson, E. A. & Petty, E. M. Conquering the complex world of human septins: implications for health and disease. Clin. Gen. 77, 511–524 (2010).

    Article  CAS  Google Scholar 

  83. Connolly, D., Abdesselam, I., Verdier-Pinard, P. & Montagna, C. Septin roles in tumorigenesis. Biol. Chem. 392, 725–738 (2011).

    Article  CAS  PubMed  Google Scholar 

  84. Estey, M. P., Di Ciano-Oliveira, C., Froese, C. D., Bejide, M. T. & Trimble, W. S. Distinct roles of septins in cytokinesis: SEPT9 mediates midbody abscission. J. Cell Biol. 191, 741–749 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Beites, C. L., Xie, H., Bowser, R. & Trimble, W. S. The septin CDCrel-1 binds syntaxin and inhibits exocytosis. Nature Neurosci. 2, 434–439 (1999).

    Article  CAS  PubMed  Google Scholar 

  86. Beites, C. L., Campbell, K. A. & Trimble, W. S. The septin Sept5/CDCrel-1 competes with α-SNAP for binding to the SNARE complex. Biochem. J. 385, 347–353 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Amin, N. D. et al. Cyclin-dependent kinase 5 phosphorylation of human septin SEPT5 (hCDCrel-1) modulates exocytosis. J. Neurosci. 28, 3631–3643 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hsu, S. C. et al. Subunit composition, protein interactions, and structures of the mammalian brain sec6/8 complex and septin filaments. Neuron 20, 1111–1122 (1998).

    Article  CAS  PubMed  Google Scholar 

  89. Vega, I. E. & Hsu, S. C. The septin protein Nedd5 associates with both the exocyst complex and microtubules and disruption of its GTPase activity promotes aberrant neurite sprouting in PC12 cells. Neuroreport 14, 31–37 (2003).

    Article  CAS  PubMed  Google Scholar 

  90. Spiliotis, E. T., Kinoshita, M. & Nelson, W. J. A mitotic septin scaffold required for mammalian chromosome congression and segregation. Science 307, 1781–1785 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhu, M. et al. Septin 7 interacts with centromere-associated protein E and is required for its kinetochore localization. J. Biol. Chem. 283, 18916–18925 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Caudron, F. & Barral, Y. Septins and the lateral compartmentalization of eukaryotic membranes. Dev. Cell 16, 493–506 (2009). Summarizes and forecasts the role of septin diffusion barriers.

    Article  CAS  PubMed  Google Scholar 

  93. Barral, Y., Mermall, V., Mooseker, M. S. & Snyder, M. Compartmentalization of the cell cortex by septins is required for maintenance of cell polarity in yeast. Mol. Cell 5, 841–851 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Takizawa, P. A., DeRisi, J. L., Wilhelm, J. E. & Vale, R. D. Plasma membrane compartmentalization in yeast by messenger RNA transport and a septin diffusion barrier. Science 290, 341–344 (2000).

    Article  CAS  PubMed  Google Scholar 

  95. Shcheprova, Z., Baldi, S., Frei, S. B., Gonnet, G. & Barral, Y. A mechanism for asymmetric segregation of age during yeast budding. Nature 454, 728–734 (2008).

    Article  CAS  PubMed  Google Scholar 

  96. Luedeke, C. et al. Septin-dependent compartmentalization of the endoplasmic reticulum during yeast polarized growth. J. Cell Biol. 169, 897–908 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Wloka, C. et al. Evidence that a septin diffusion barrier is dispensable for cytokinesis in budding yeast. Biol. Chem. 392, 813–829 (2011).

    Article  CAS  PubMed  Google Scholar 

  98. De Vos, K. J., Allan, V. J., Grierson, A. J. & Sheetz, M. P. Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission. Curr. Biol. 15, 678–683 (2005).

    Article  CAS  PubMed  Google Scholar 

  99. Singla, V. & Reiter, J. F. The primary cilium as the cell's antenna: signaling at a sensory organelle. Science 313, 629–633 (2006).

    Article  CAS  PubMed  Google Scholar 

  100. Cossart, P. & Sansonetti, P. J. Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304, 242–248 (2004).

    Article  CAS  PubMed  Google Scholar 

  101. Gouin, E., Welch, M. D. & Cossart, P. Actin-based motility of intracellular pathogens. Curr. Opin. Microbiol. 8, 35–45 (2005).

    Article  CAS  PubMed  Google Scholar 

  102. Haglund, C. M. & Welch, M. D. Pathogens and polymers: microbe–host interactions illuminate the cytoskeleton. J. Cell Biol. 195, 7–17 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Loisel, T. P., Boujemaa, R., Pantaloni, D. & Carlier, M. F. Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Nature 401, 613–616 (1999).

    Article  CAS  PubMed  Google Scholar 

  104. Van Troys, M. et al. The actin propulsive machinery: the proteome of Listeria monocytogenes tails. Biochem. Biophys. Res. Commun. 375, 194–199 (2008).

    Article  CAS  PubMed  Google Scholar 

  105. Marchiando, A. M., Graham, W. V. & Turner, J. R. Epithelial barriers in homeostasis and disease. Annu. Rev. Pathol. 5, 119–144 (2010).

    Article  CAS  PubMed  Google Scholar 

  106. Mostowy, S. et al. p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways. J. Biol. Chem. 286, 26987–26995 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kechad, A., Jananji, S., Ruella, Y. & Hickson, G. R. X. Anillin acts as a bifunctional linker coordinating midbody ring biogenesis during cytokinesis. Curr. Biol. 5 Jan 2012 (doi:10.1016/j.cub.2011.11.062).

    Article  CAS  PubMed  Google Scholar 

  108. Hickson, G. R. X. & O'Farrell, P. H. Rho-dependent control of anillin behavior during cytokinesis. J. Cell Biol. 180, 285–294 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Ogawa, M. et al. Escape of intracellular Shigella from autophagy. Science 307, 727–731 (2005).

    Article  CAS  PubMed  Google Scholar 

  110. Yoshikawa, Y. et al. Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nature Cell Biol. 11, 1233–1240 (2009).

    Article  CAS  PubMed  Google Scholar 

  111. Ribet, D. & Cossart, P. Pathogen-mediated posttranslational modifications: a re-emerging field. Cell 143, 694–702 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Tooze, S. A. & Yoshimori, T. The origin of the autophagosomal membrane. Nature Cell Biol. 12, 831–835 (2010).

    Article  CAS  PubMed  Google Scholar 

  113. Ravikumar, B., Moreau, K., Jahreiss, L., Puri, C. & Rubinsztein, D. C. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nature Cell Biol. 12, 1021–1021 (2010).

    Article  CAS  Google Scholar 

  114. Reggiori, F. & Tooze, S. A. The emERgence of autophagosomes. Dev. Cell 17, 747–748 (2009).

    Article  CAS  PubMed  Google Scholar 

  115. Hailey, D. W. et al. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141, 656–667 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Sal-Man, N., Biemans-Oldehinkel, E. & Finlay, B. B. Structural microengineers: pathogenic Escherichia coli redesigns the actin cytoskeleton in host cells. Structure 17, 15–19 (2009).

    Article  CAS  PubMed  Google Scholar 

  117. Kumar, Y. & Valdivia, R. H. Actin and intermediate filaments stabilize the Chlamydia trachomatis vacuole by forming dynamic structural scaffolds. Cell Host Microbe 4, 159–169 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Cabeen, M. T. & Jacobs-Wagner, C. The bacterial cytoskeleton. Annu. Rev. Gen. 44, 365–392 (2010).

    Article  CAS  Google Scholar 

  119. Nair, U. et al. SNARE proteins are required for macroautophagy. Cell 146, 290–302 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Moreau, K., Ravikumar, B., Renna, M., Puri, C. & Rubinsztein, D. C. Autophagosome precursor maturation requires homotypic fusion. Cell 146, 303–317 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Lee, J. Y. et al. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J. 29, 969–980 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Mizushima, N., Yoshimori, T. & Ohsumi, Y. The role of ATG proteins in autophagosome formation. Annu. Rev. Cell Dev. Biol. 27, 107–132 (2011).

    Article  CAS  PubMed  Google Scholar 

  123. Nakatogawa, H., Suzuki, K., Kamada, Y. & Ohsumi, Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nature Rev. Mol. Cell Biol. 10, 458–467 (2009).

    Article  CAS  Google Scholar 

  124. Levine, B., Mizushima, N. & Virgin, H. W. Autophagy in immunity and inflammation. Nature 469, 323–335 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Mizushima, N. & Komatsu, M. Autophagy: renovation of cells and tissues. Cell 147, 728–741 (2011).

    Article  CAS  PubMed  Google Scholar 

  126. Hall, P. A. & Finger, F. P. in The Septins (eds Hall, P. A., Russell, S. E. H. & Pringle, J. R.) 295–317 (Wiley-Blackwell, 2008).

    Book  Google Scholar 

  127. Hall, P. A. & Russell, S. E. H. The pathobiology of the septin gene family. J. Pathol. 204, 489–505 (2004).

    Article  CAS  PubMed  Google Scholar 

  128. Estey, M. P., Kim, M. S. & Trimble, W. S. Septins. Curr. Biol. 21, R384–R387 (2011).

    Article  CAS  PubMed  Google Scholar 

  129. Lee, J. E. et al. CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium. Nature Genet. 15 Jan 2012 (doi: 10.1038/ng.1078)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Rubinsztein, D. C., Shpilka, T. & Elazar, Z. Mechanisms of autophagosome biogenesis. Curr. Biol. 22 R29–R34 (2012).

    Article  CAS  PubMed  Google Scholar 

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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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  1. Serge Mostowy

    Present address: Present address: Section of Microbiology, Centre for Molecular Microbiology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.,

Authors and Affiliations

  1. Département de Biologie Cellulaire et Infection, Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, F-75015, France

    Serge Mostowy & Pascale Cossart

  2. Inserm, U604, Paris, F-75015, France

    Serge Mostowy & Pascale Cossart

  3. INRA, USC2020, Paris, F-75015, France

    Serge Mostowy & Pascale Cossart

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  1. Serge Mostowy
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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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