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Membrane budding and scission by the ESCRT machinery: it's all in the neck

Nature Reviews Molecular Cell Biology volume 11, pages 556–566 (2010)Cite this article

Subjects

This article has been updated

Key Points

  • Endosomal sorting complexes required for transport (ESCRTs) are required for the lysosomal degradation of plasma membrane proteins, budding of most enveloped viruses, cytokinesis and autophagy.

  • ESCRT-I and ESCRT-II work together to bud membranes away from the cytosol by stabilizing the neck of the bud.

  • ESCRT-III forms helical assemblies that sever membrane necks from within.

  • The AAA+ ATPase vacuolar protein sorting 4 (Vps4) forms a dodecameric assembly together with Vta1 that solubilizes and recycles membrane-bound ESCRT-III following membrane scission.

Abstract

The endosomal sorting complexes required for transport (ESCRTs) catalyse one of the most unusual membrane remodelling events in cell biology. ESCRT-I and ESCRT-II direct membrane budding away from the cytosol by stabilizing bud necks without coating the buds and without being consumed in the buds. ESCRT-III cleaves the bud necks from their cytosolic faces. ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis and, probably, autophagy. Recent studies of ultrastructures induced by ESCRT-III overexpression in cells and the in vitro reconstitution of the budding and scission reactions have led to breakthroughs in understanding these remarkable membrane reactions.

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Figure 1: Biological roles of the ESCRTs.
Figure 2: ESCRT-I and ESCRT-II.
Figure 3: ESCRT-III.
Figure 4: Membrane budding by ESCRTs.
Figure 5: Membrane scission by ESCRT-III.
Figure 6: VPS4 structure and function.

Change history

  • 04 August 2010

    In the version of the article that was previously published there was a mistake in the legend to figure 4. The membrane is labelled with rhodamine-tagged phosphatidylethanolamine and not rhodamine-tagged phycoerythrin as stated. The error has been corrected online.

References

  1. Sorkin, A. & von Zastrow, M. Endocytosis and signalling: intertwining molecular networks. Nature Rev. Mol. Cell Biol. 10, 609–622 (2009).

    CAS  Google Scholar 

  2. Gruenberg, J. & Stenmark, H. The biogenesis of multivesicular endosomes. Nature Rev. Mol. Cell Biol. 5, 317–323 (2004).

    CAS  Google Scholar 

  3. Russell, M. R. G., Nickerson, D. P. & Odorizzi, G. Molecular mechanisms of late endosome morphology, identity and sorting. Curr. Opin. Cell Biol. 18, 422–428 (2006).

    CAS  PubMed  Google Scholar 

  4. Piper, R. C. & Katzmann, D. J. Biogenesis and function of multivesicular bodies. Annu. Rev. Cell Devel. Biol. 23, 519–547 (2007).

    CAS  Google Scholar 

  5. Peplowska, K., Markgraf, D. F., Ostrowicz, C. W., Bange, G. & Ungermann, C. The CORVET tethering complex interacts with the yeast Rab5 homolog Vps21 and is involved in endo-lysosomal biogenesis. Dev. Cell 12, 739–750 (2007).

    CAS  PubMed  Google Scholar 

  6. Pucadyil, T. J. & Schmid, S. L. Conserved functions of membrane active GTPases in coated vesicle formation. Science 325, 1217–1220 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Raymond, C. K., Howald-Stevenson, I., Vater, C. A. & Stevens, T. H. Morphological classification of the yeast vacuolar protein sorting mutants — evidence for a prevacuolar compartment in class-E Vps mutants. Mol. Biol. Cell 3, 1389–1402 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Babst, M., Katzmann, D. J., Snyder, W. B., Wendland, B. & Emr, S. D. Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev. Cell 3, 283–289 (2002).

    CAS  PubMed  Google Scholar 

  9. Babst, M., Katzmann, D. J., Estepa-Sabal, E. J., Meerloo, T. & Emr, S. D. ESCRT-III: an endosome-associated heterooligomeric protein complex required for MVB sorting. Dev. Cell 3, 271–282 (2002).

    CAS  PubMed  Google Scholar 

  10. Katzmann, D. J., Babst, M. & Emr, S. D. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106, 145–155 (2001).

    CAS  PubMed  Google Scholar 

  11. Spitzer, C. et al. The Arabidopsis elch mutant reveals functions of an ESCRT component in cytokinesis. Development 133, 4679–4689 (2006).

    CAS  PubMed  Google Scholar 

  12. Carlton, J. G. & Martin-Serrano, J. Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science 316, 1908–1912 (2007).

    CAS  PubMed  Google Scholar 

  13. Morita, E. et al. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J. 26, 4215–4227 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Morita, E. & Sundquist, W. I. Retrovirus budding. Annu. Rev. Cell Devel. Biol. 20, 395–425 (2004).

    CAS  Google Scholar 

  15. Fujii, K., Hurley, J. H. & Freed, E. O. Beyond Tsg101: the role of Alix in 'ESCRTing' HIV-1. Nature Rev. Microbiol. 5, 912–916 (2007).

    CAS  Google Scholar 

  16. Filimonenko, M. et al. Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J. Cell Biol. 179, 485–500 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Lee, J. A., Beigneux, A., Ahmad, S. T., Young, S. G. & Gao, F. B. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr. Biol. 17, 1561–1567 (2007).

    CAS  PubMed  Google Scholar 

  18. Rieder, S. E., Banta, L. M., Kohrer, K., McCaffery, J. M. & Emr, S. D. Multilamellar endosome-like compartment accumulates in the yeast Vps28 vacuolar protein sorting mutant. Mol. Biol. Cell 7, 985–999 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Nickerson, D. P., West, M. & Odorizzi, G. Did2 coordinates Vps4-mediated dissociation of ESCRT-III from endosomes. J. Cell Biol. 175, 715–720 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Nickerson, D. P., West, M., Henry, R. & Odorizzi, G. Regulators of Vps4 activity at endosomes differentially influence the size and rate of formation of intralumenal vesicles. Mol. Biol. Cell 21, 1023–1032 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Hanson, P. I., Roth, R., Lin, Y. & Heuser, J. E. Plasma membrane deformation by circular arrays of ESCRT-III protein filaments. J. Cell Biol. 180, 389–402 (2008). Using EM of ESCRT-III proteins overexpressed in cultured mammalian cells, this study shows that SNF7 assembles into circular filaments that can be induced to create or stabilize negative curvature in buds and tubules that deform the membrane away from the cytoplasm.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Lata, S. et al. Helical structures of ESCRT-III are disassembled by VPS4. Science 321, 1354–1357 (2008). Reports the reconstitution of a tubular ESCRT-III structure from human VPS24 and VPS2, and shows that VPS4 can disassemble it from the inner surface of the tube.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Pires, R. et al. A crescent-shaped ALIX dimer targets ESCRT-III CHMP4 filaments. Structure 17, 843–856 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Bajorek, M. et al. Structural basis for ESCRT-III protein autoinhibition. Nature Struct. Mol. Biol. 16, 754–762 (2009).

    CAS  Google Scholar 

  25. Wollert, T., Wunder, C., Lippincott-Schwartz, J. & Hurley, J. H. Membrane scission by the ESCRT-III complex. Nature 458, 172–177 (2009). Shows that the three earliest-assembling subunits of ESCRT-III — Vps20, Snf7 and Vps24 — have an intrinsic membrane scission activity. The fourth subunit, Vps2, is not required for scission, but is required for coupling to Vps4. Also shows that the AAA+ ATPase Vps4 is required for recycling ESCRT-III but not for scission.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Im, Y. J., Wollert, T., Boura, E. & Hurley, J. H. Structure and function of the ESCRT-II–III interface in multivesicular body biogenesis. Dev. Cell 17, 234–243 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Wollert, T. & Hurley, J. H. Molecular mechanism of multivesicular body biogenesis by the ESCRT complexes. Nature 464, 864–869 (2010). Reveals that ESCRT-I and ESCRT-II work together to induce membrane budding through assembly at the bud neck. This assembly recruits ESCRT-III selectively to the membrane neck, thus ensuring that the ESCRTs are consumed in the ILV.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Lenz, M., Crow, D. J. G. & Joanny, J. F. Membrane buckling induced by curved filaments. Phys. Rev. Lett. 103, 038101 (2009).

    PubMed  Google Scholar 

  29. Fabrikant, G. et al. Computational model of membrane fission catalyzed by ESCRT-III. PLOS Comp. Biol. 5, e1000575 (2009). This computational analysis of the energetics of membrane scission shows that the experimentally determined membrane affinity of ESCRT-III, when incorporated into an assembly of realistic dimensions, is sufficient to provide the energy required for membrane scission.

    Google Scholar 

  30. Raiborg, C. & Stenmark, H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458, 445–452 (2009).

    CAS  PubMed  Google Scholar 

  31. Hanson, P. I., Shim, S. & Merrill, S. A. Cell biology of the ESCRT machinery. Curr. Opin. Cell Biol. 21, 568–574 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Carlton, J. G. & Martin-Serrano, J. The ESCRT machinery: new functions in viral and cellular biology. Biochem. Soc. Trans. 37, 195–199 (2009).

    CAS  PubMed  Google Scholar 

  33. Hurley, J. H. & Emr, S. D. The ESCRT complexes: structure and mechanism of a membrane-trafficking network. Annu. Rev. Biophys. Biomol. Struct. 35, 277–298 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Saksena, S., Sun, J., Chu, T. & Emr, S. D. ESCRTing proteins in the endocytic pathway. Trends. Biochem. Sci. 32, 561–573 (2007).

    CAS  PubMed  Google Scholar 

  35. Williams, R. L. & Urbe, S. The emerging shape of the ESCRT machinery. Nature Rev. Mol. Cell Biol. 8, 355–368 (2007).

    CAS  Google Scholar 

  36. Hurley, J. H. ESCRT complexes and the biogenesis of multivesicular bodies. Curr. Opin. Cell Biol. 20, 4–11 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Stuffers, S., Brech, A. & Stenmark, H. ESCRT proteins in physiology and disease. Exp. Cell Res. 315, 1619–1626 (2009).

    CAS  PubMed  Google Scholar 

  38. Chu, T., Sun, J., Saksena, S. & Emr, S. D. New component of ESCRT-I regulates endosomal sorting complex assembly. J. Cell Biol. 175, 815–823 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Oestreich, A. J., Davies, B. A., Payne, J. A. & Katzmann, D. J. Mvb12 is a novel member of ESCRT-I involved in cargo selection by the multivesicular body pathway. Mol. Biol. Cell 18, 646–657 (2006).

    PubMed  Google Scholar 

  40. Curtiss, M., Jones, C. & Babst, M. Efficient cargo sorting by ESCRT-I and the subsequent release of ESCRT-I from multivesicular bodies requires the subunit Mvb12. Mol. Biol. Cell 18, 636–645 (2006).

    PubMed  Google Scholar 

  41. Kostelansky, M. S. et al. Molecular architecture and functional model of the complete yeast ESCRT-I heterotetramer. Cell 129, 485–498 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Katzmann, D. J., Stefan, C. J., Babst, M. & Emr, S. D. Vps27 recruits ESCRT machinery to endosomes during MVB sorting. J. Cell Biol. 162, 413–423 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Bilodeau, P. S., Winistorfer, S. C., Kearney, W. R., Robertson, A. D. & Piper, R. C. Vps27–Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome. J. Cell Biol. 163, 237–243 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Pornillos, O. et al. HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein. J. Cell Biol. 162, 425–434 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Bieniasz, P. D. The cell biology of HIV-1 virion genesis. Cell Host Microbe 5, 550–558 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Teo, H., Veprintsev, D. B. & Williams, R. L. Structural insights into endosomal sorting complex required for transport (ESCRT-I) recognition of ubiquitinated proteins. J. Biol. Chem. 279, 28689–28696 (2004).

    CAS  PubMed  Google Scholar 

  47. Sundquist, W. I. et al. Ubiquitin recognition by the human TSG101 protein. Mol. Cell 13, 783–789 (2004).

    CAS  PubMed  Google Scholar 

  48. Shields, S. B. et al. ESCRT ubiquitin binding domains function cooperatively during MVB cargo sorting. J. Cell Biol. 185, 213–224 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Lee, H. H., Elia, N., Ghirlando, R., Lippincott-Schwartz, J. & Hurley, J. H. Midbody targeting of the ESCRT machinery by a noncanonical coiled coil in CEP55. Science 322, 576–580 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Kostelansky, M. S. et al. Structural and functional organization of the ESCRT-I trafficking complex. Cell 125, 113–126 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Gill, D. J. et al. Structural insight into the ESCRT-I/-II link and its role in MVB trafficking. EMBO J. 26, 600–612 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Teo, H. L. et al. ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes. Cell 125, 99–111 (2006).

    CAS  PubMed  Google Scholar 

  53. Hierro, A. et al. Structure of the ESCRT-II endosomal trafficking complex. Nature 431, 221–225 (2004).

    CAS  PubMed  Google Scholar 

  54. Teo, H., Perisic, O., Gonzalez, B. & Williams, R. L. ESCRT-II, an endosome-associated complex required for protein sorting: crystal structure and interactions with ESCRT-III and membranes. Dev. Cell 7, 559–569 (2004).

    CAS  PubMed  Google Scholar 

  55. Im, Y. J. & Hurley, J. H. Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex. Dev. Cell 14, 902–913 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Teis, D., Saksena, S., Judson, B. L. & Emr, S. D. ESCRT-II coordinates the assembly of ESCRT-III filaments for cargo sorting and multivesicular body vesicle formation. EMBO J. 29, 871–883 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Saksena, S., Wahlman, J., Teis, D., Johnson, A. E. & Emr, S. D. Functional reconstitution of ESCRT-III assembly and disassembly. Cell 136, 97–109 (2009). Elegantly shows by fluorescence spectroscopy that Vps20 and Snf7 undergo a series of conformational changes as ESCRT-III polymerizes on membranes.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Alam, S. L. et al. Ubiquitin interactions of NZF zinc fingers. EMBO J. 23, 1411–1421 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Slagsvold, T. et al. Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J. Biol. Chem. 280, 19600–19606 (2005).

    CAS  PubMed  Google Scholar 

  60. Alam, S. L. et al. Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain. Nature Struct. Mol. Biol. 13, 1029–1030 (2006).

    CAS  Google Scholar 

  61. Hirano, S. et al. Structural basis of ubiquitin recognition by mammalian Eap45 GLUE domain. Nature Struct. Mol. Biol. 13, 1031–1032 (2006).

    CAS  Google Scholar 

  62. Teis, D., Saksena, S. & Emr, S. D. Ordered assembly of the ESCRT-III complex on endosomes is required to sequester cargo during MVB formation. Dev. Cell 15, 578–589 (2008). Defines the order in which ESCRT-III proteins are recruited to the endosome in yeast as Vps20, Snf7, Vps24 and Vps2, and quantifies their relative abundance. Snf7 is the most abundant ESCRT-III protein in yeast and is shown by Förster resonance energy transfer to interact with itself.

    CAS  PubMed  Google Scholar 

  63. Muziol, T. et al. Structural basis for budding by the ESCRT-III factor CHMP3. Dev. Cell 10, 821–830 (2006).

    CAS  PubMed  Google Scholar 

  64. Xiao, J. Y. et al. Structural basis of Ist1 function and Ist1–Did2 interaction in the multivesicular body pathway and cytokinesis. Mol. Biol. Cell 20, 3514–3524 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Zamborlini, A. et al. Release of autoinhibition converts ESCRT-III components into potent inhibitors of HIV-1 budding. Proc. Natl Acad. Sci. USA 103, 19140–19145 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Shim, S., Kimpler, L. A. & Hanson, P. I. Structure/function analysis of four core ESCRT-III proteins reveals common regulatory role for extreme C-terminal domain. Traffic 8, 1068–1079 (2007).

    CAS  PubMed  Google Scholar 

  67. Murk, J. L. A. N. et al. Endosomal compartmentalization in three dimensions: implications for membrane fusion. Proc. Natl Acad. Sci. USA 100, 13332–13337 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Langelier, C. et al. Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release. J. Virol. 80, 9465–9480 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Bajorek, M. et al. Biochemical analyses of human IST1 and its function in cytokinesis. Mol. Biol. Cell 20, 1360–1373 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Ghazi-Tabatabai, S. et al. Structure and disassembly of filaments formed by the ESCRT-III subunit Vps24. Structure 16, 1345–1356 (2008).

    CAS  PubMed  Google Scholar 

  71. Babst, M., Sato, T. K., Banta, L. M. & Emr, S. D. Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p. EMBO J. 16, 1820–1831 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Babst, M., Wendland, B., Estepa, E. J. & Emr, S. D. The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function. EMBO J. 17, 2982–2993 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Scott, A. et al. Structural and mechanistic studies of VPS4 proteins. EMBO J. 24, 3658–3669 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Yu, Z. H., Gonciarz, M. D., Sundquist, W. I., Hill, C. P. & Jensen, G. J. Cryo-EM structure of dodecameric Vps4p and its 2:1 complex with Vta1p. Mol. Biol. 377, 364–377 (2008).

    CAS  Google Scholar 

  75. Gonciarz, M. D. et al. Biochemical and structural studies of yeast Vps4 oligomerization. J. Mol. Biol. 384, 878–895 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Hartmann, C. et al. Vacuolar protein sorting: two different functional states of the AAA-ATPase Vps4p. J. Mol. Biol. 377, 352–363 (2008).

    CAS  PubMed  Google Scholar 

  77. Landsberg, M. J., Vajjhala, P. R., Rothnagel, R., Munn, A. L. & Hankamer, B. Three-dimensional structure of AAA ATPase Vps4: advancing structural insights into the mechanisms of endosomal sorting and enveloped virus budding. Structure 17, 427–437 (2009).

    CAS  PubMed  Google Scholar 

  78. Inoue, M. et al. Nucleotide-dependent conformational changes and assembly of the AAA ATPase SKD1/VPS4B. Traffic 9, 2180–2189 (2008).

    CAS  PubMed  Google Scholar 

  79. Obita, T. et al. Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4. Nature 449, 735–739 (2007).

    CAS  PubMed  Google Scholar 

  80. Stuchell-Brereton, M. et al. ESCRT-III recognition by VPS4 ATPases. Nature 449, 740–744 (2007).

    CAS  PubMed  Google Scholar 

  81. Kieffer, C. et al. Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding. Dev. Cell 15, 62–73 (2008). Together with references 73 and 74, references 79–81 provide the main structural underpinnings for the Vps4 disassembly mechanism. Reference 74 shows that the two hexameric rings of Vps4 are asymmetric, and reference 73 shows that central pore residues are important for function. References 79–81 show how Vps4 binds its ESCRT-III substrates.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Azmi, I. F. et al. ESCRT-III family members stimulate Vps4 ATPase activity directly or via Vta1. Dev. Cell 14, 50–61 (2008).

    CAS  PubMed  Google Scholar 

  83. Xiao, J. et al. Structural basis of Vta1 function in the multi-vesicular body sorting pathway. Dev. Cell 14, 37–49 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Rue, S. M., Mattei, S., Saksena, S. & Emr, S. D. Novel Ist1–Did2 complex functions at a late step in multivesicular body sorting. Mol. Biol. Cell 19, 475–484 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Dimaano, C., Jones, C. B., Hanono, A., Curtiss, M. & Babst, M. Ist1 regulates Vps4 localization and assembly. Mol. Biol. Cell 19, 465–474 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Shestakova, A. et al. Assembly of the AAA ATPase Vps4 on ESCRT-III. Mol. Biol. Cell 21, 1059–1071 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Barkow, S. R., Levchenko, I., Baker, T. A. & Sauer, R. T. Polypeptide translocation by the AAA plus ClpXP protease machine. Chem. Biol. 16, 605–612 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Samson, R. Y., Obita, T., Freund, S. M., Williams, R. L. & Bell, S. D. A role for the ESCRT system in cell division in Archaea. Science 322, 1710–1713 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Lindas, A. C., Karlsson, E. A., Lindgren, M. T., Ettema, T. J. G. & Bernander, R. A unique cell division machinery in the Archaea. Proc. Natl Acad. Sci. USA 105, 18942–18946 (2008). References 88 and 89 show that in the hyperthermophilic Crenarchaeota, ancient homologues of ESCRT-III and Vps4 are required for the completion of cell division. Crenarchaeota lack homologues of ESCRT-0–ESCRT-II, so these studies strongly suggest that ESCRT-III and Vps4 might be the minimal membrane scission machinery.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Carlton, J. G., Agromayor, M. & Martin-Serrano, J. Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release. Proc. Natl Acad. Sci. USA 105, 10541–10546 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Steigemann, P. & Gerlich, D. W. Cytokinetic abscission: cellular dynamics at the midbody. Trends Cell Biol. 19, 606–616 (2009).

    CAS  PubMed  Google Scholar 

  92. Yang, D. et al. Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B. Nature Struct. Mol. Biol. 15, 1278–1286 (2008).

    CAS  Google Scholar 

  93. Connell, J. W., Lindon, C., Luzio, J. P. & Reid, E. Spastin couples microtubule severing to membrane traffic in completion of cytokinesis and secretion. Traffic 10, 42–56 (2009).

    CAS  PubMed  Google Scholar 

  94. Chen, B. J. & Lamb, R. A. Mechanisms for enveloped virus budding: can some viruses do without an ESCRT? Virology 372, 221–232 (2008).

    CAS  PubMed  Google Scholar 

  95. Jouvenet, N., Bieniasz, P. D. & Simon, S. M. Imaging the biogenesis of individual HIV-1 virions in live cells. Nature 454, 236–240 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Ivanchenko, S. et al. Dynamics of HIV-1 assembly and release. PloS Pathog. 5, e1000652 (2009).

    PubMed  PubMed Central  Google Scholar 

  97. Carlson, L. A. et al. Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis. Cell Host Microbe 4, 592–599 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Kim, J. et al. Structural basis for endosomal targeting by the Bro1 domain. Dev. Cell 8, 937–947 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Fisher, R. D. et al. Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. Cell 128, 841–852 (2007).

    CAS  PubMed  Google Scholar 

  100. Usami, Y., Popov, S. & Gottlinger, H. G. Potent rescue of human immunodeficiency virus type 1 late domain mutants by ALIX/AIP1 depends on its CHMP4 binding site. J. Virol. 81, 6614–6622 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. McCullough, J. et al. ALIX-CHMP4 interactions in the human ESCRT pathway. Proc. Natl Acad. Sci. USA 105, 7687–7691 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Mizushima, N., Levine, B., Cuervo, A. M. & Klionsky, D. J. Autophagy fights disease through cellular self-digestion. Nature 451, 1069–1075 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Rusten, T. E. & Stenmark, H. How do ESCRT proteins control autophagy? J. Cell Sci. 122, 2179–2183 (2009).

    CAS  PubMed  Google Scholar 

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Acknowledgements

Research in the Hurley laboratory is supported by the intramural program of the National Institutes of Health, The National Institute of Diabetes and Digestive and Kidney Diseases and the Intramural AIDS Targeted Antiretroviral Program. Research in the Hanson laboratory is supported by grants from the National Institutes of Health and the American Heart Association. Both authors thank the members of their laboratories and other colleagues for helpful discussions.

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  1. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892-0580, Maryland, USA

    James H. Hurley

  2. Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, 63110, Missouri, USA

    Phyllis I. Hanson

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Glossary

Lysosome

A cellular organelle in metazoa that is primarily responsible for degradation of unneeded or harmful materials and their recycling into biosynthetic precursors.

AAA+ ATPase

A protein belonging to a family of ATPases associated with diverse cellular activities. Each enzyme contains one or two AAA motifs of 230 to 250 amino acids, including the Walker homology sequences of P-loop ATPases and regions of similarity that are unique to AAA proteins.

Autophagy

Used here to refer to macroautophagy, the process of envelopment of the cytosol and other material by the phagophore, which subsequently fuses with the lysosome.

GUV

A synthetic vesicle of 5–50 μm in size that is useful for visualizing membrane deformation by fluorescence microscopy.

Ubiquitin

A conserved 76 amino acid protein that is covalently attached through its C terminus to Lys residues of many proteins, including proteins trafficked to MVBs by ESCRTs.

Gag protein

The protein product of the HIV-1 gag gene, consisting of four functional segments: MA, CA, NC and p6. The p6 segment contains the motifs PTAP and YPXL, which bind to ESCRT-I and ALIX, respectively.

Midbody

A dense protein structure located at the centre of the narrow membrane neck that connects two dividing cells.

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Hurley, J., Hanson, P. Membrane budding and scission by the ESCRT machinery: it's all in the neck. Nat Rev Mol Cell Biol 11, 556–566 (2010). https://doi.org/10.1038/nrm2937

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