Molecular Mechanisms of the Membrane Sculpting ESCRT Pathway

Overview

Journal Cold Spring Harb Perspect Biol

Specialties Biology
Molecular Biology

Date 2013 Sep 5

PMID 24003212

Citations 244

Authors

William Mike Henne

Harald Stenmark

Scott D Emr

Affiliations

Soon will be listed here.

Abstract

The endosomal sorting complexes required for transport (ESCRT) drive multivesicular body (MVB) biogenesis and cytokinetic abscission. Originally identified through genetics and cell biology, more recent work has begun to elucidate the molecular mechanisms of ESCRT-mediated membrane remodeling, with special focus on the ESCRT-III complex. In particular, several light and electron microscopic studies provide high-resolution imaging of ESCRT-III rings and spirals that purportedly drive MVB morphogenesis and abscission. These studies highlight unifying principles to ESCRT-III function, in particular: (1) the ordered assembly of the ESCRT-III monomers into a heteropolymer, (2) ESCRT-III as a dynamic complex, and (3) the role of the AAA ATPase Vps4 as a contributing factor in membrane scission. Mechanistic comparisons of ESCRT-III function in MVB morphogenesis and cytokinesis suggest common mechanisms in membrane remodeling.

Citing Articles

Roles for Exosomes in the Pathogenesis, Drug Delivery and Therapy of Psoriasis.

Chen Y, Liu H, He Y, Yang B, Lu W, Dai Z Pharmaceutics. 2025; 17(1).

PMID: 39861699 PMC: 11768235. DOI: 10.3390/pharmaceutics17010051.

Advances in the treatment of liver injury based on mesenchymal stem cell-derived exosomes.

Hu C, Wang L Stem Cell Res Ther. 2024; 15(1):474.

PMID: 39696473 PMC: 11657567. DOI: 10.1186/s13287-024-04087-3.

The role of small extracellular vesicles in spreading and inhibiting arthropod-borne diseases.

Owliaee I, Khaledian M, Shojaeian A, Boroujeni A GMS Hyg Infect Control. 2024; 19:Doc48.

PMID: 39553300 PMC: 11565596. DOI: 10.3205/dgkh000503.

Construction of a prognostic model with exosome biogenesis- and release-related genes and identification of RAB27B in immune infiltration of pancreatic cancer.

Li T, Qin C, Zhao B, Li Z, Wang Y, Zhao Y Transl Cancer Res. 2024; 13(9):4846-4865.

PMID: 39430819 PMC: 11483359. DOI: 10.21037/tcr-24-54.

Exosomes in nanomedicine: a promising cell-free therapeutic intervention in burn wounds.

Manzoor T, Farooq N, Sharma A, Shiekh P, Hassan A, Dar L Stem Cell Res Ther. 2024; 15(1):355.

PMID: 39385310 PMC: 11462792. DOI: 10.1186/s13287-024-03970-3.

References

Katzmann D, Babst M, Emr S . Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell. 2001; 106(2):145-55. DOI: 10.1016/s0092-8674(01)00434-2. View

Dowlatshahi D, Sandrin V, Vivona S, Shaler T, Kaiser S, Melandri F . ALIX is a Lys63-specific polyubiquitin binding protein that functions in retrovirus budding. Dev Cell. 2012; 23(6):1247-54. PMC: 3522770. DOI: 10.1016/j.devcel.2012.10.023. View

Agromayor M, Carlton J, Phelan J, Matthews D, Carlin L, Ameer-Beg S . Essential role of hIST1 in cytokinesis. Mol Biol Cell. 2009; 20(5):1374-87. PMC: 2649264. DOI: 10.1091/mbc.e08-05-0474. View

Wollert T, Wunder C, Lippincott-Schwartz J, Hurley J . Membrane scission by the ESCRT-III complex. Nature. 2009; 458(7235):172-7. PMC: 2743992. DOI: 10.1038/nature07836. View

Spitzer C, Schellmann S, Sabovljevic A, Shahriari M, Keshavaiah C, Bechtold N . The Arabidopsis elch mutant reveals functions of an ESCRT component in cytokinesis. Development. 2006; 133(23):4679-89. DOI: 10.1242/dev.02654. View

Martinelli N, Hartlieb B, Usami Y, Sabin C, Dordor A, Miguet N . CC2D1A is a regulator of ESCRT-III CHMP4B. J Mol Biol. 2012; 419(1-2):75-88. PMC: 3433253. DOI: 10.1016/j.jmb.2012.02.044. View

Carlton J, Martin-Serrano J . Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science. 2007; 316(5833):1908-12. DOI: 10.1126/science.1143422. View

Raiborg C, Bremnes B, Mehlum A, Gillooly D, DArrigo A, Stang E . FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes. J Cell Sci. 2001; 114(Pt 12):2255-63. DOI: 10.1242/jcs.114.12.2255. View

Boucrot E, Pick A, Camdere G, Liska N, Evergren E, McMahon H . Membrane fission is promoted by insertion of amphipathic helices and is restricted by crescent BAR domains. Cell. 2012; 149(1):124-36. PMC: 3465558. DOI: 10.1016/j.cell.2012.01.047. View

10.

Bajorek M, Schubert H, McCullough J, Langelier C, Eckert D, Stubblefield W . Structural basis for ESCRT-III protein autoinhibition. Nat Struct Mol Biol. 2009; 16(7):754-62. PMC: 2712734. DOI: 10.1038/nsmb.1621. View

11.

Teo H, Gill D, Sun J, Perisic O, Veprintsev D, Vallis Y . ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes. Cell. 2006; 125(1):99-111. DOI: 10.1016/j.cell.2006.01.047. View

12.

Babst M . MVB vesicle formation: ESCRT-dependent, ESCRT-independent and everything in between. Curr Opin Cell Biol. 2011; 23(4):452-7. PMC: 3148405. DOI: 10.1016/j.ceb.2011.04.008. View

13.

Morita E, Sandrin V, McCullough J, Katsuyama A, Baci Hamilton I, Sundquist W . ESCRT-III protein requirements for HIV-1 budding. Cell Host Microbe. 2011; 9(3):235-242. PMC: 3070458. DOI: 10.1016/j.chom.2011.02.004. View

14.

Lee S, Chang J, Renvoise B, Tipirneni A, Yang S, Blackstone C . MITD1 is recruited to midbodies by ESCRT-III and participates in cytokinesis. Mol Biol Cell. 2012; 23(22):4347-61. PMC: 3496609. DOI: 10.1091/mbc.E12-04-0292. View

15.

Hadders M, Agromayor M, Obita T, Perisic O, Caballe A, Kloc M . ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes. Proc Natl Acad Sci U S A. 2012; 109(43):17424-9. PMC: 3491508. DOI: 10.1073/pnas.1206839109. View

16.

Stachowiak J, Schmid E, Ryan C, Ann H, Sasaki D, Sherman M . Membrane bending by protein-protein crowding. Nat Cell Biol. 2012; 14(9):944-9. DOI: 10.1038/ncb2561. View

17.

Henne W, Buchkovich N, Emr S . The ESCRT pathway. Dev Cell. 2011; 21(1):77-91. DOI: 10.1016/j.devcel.2011.05.015. View

18.

Carlton J, Caballe A, Agromayor M, Kloc M, Martin-Serrano J . ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C. Science. 2012; 336(6078):220-5. PMC: 3998087. DOI: 10.1126/science.1217180. View

19.

Garrus J, von Schwedler U, Pornillos O, Morham S, Zavitz K, Wang H . Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell. 2001; 107(1):55-65. DOI: 10.1016/s0092-8674(01)00506-2. View

20.

Hanson P, Roth R, Lin Y, Heuser J . Plasma membrane deformation by circular arrays of ESCRT-III protein filaments. J Cell Biol. 2008; 180(2):389-402. PMC: 2213594. DOI: 10.1083/jcb.200707031. View