Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Feb:38:1-11.
doi: 10.1016/j.ceb.2015.12.001. Epub 2016 Jan 15.

The ESCRT machinery: new roles at new holes

Y Olmos  1 , J G Carlton  2
Affiliations
Review

The ESCRT machinery: new roles at new holes

Y Olmos et al. Curr Opin Cell Biol. 2016 Feb.

Abstract

The ESCRT machinery drives a diverse collection of membrane remodeling events, including multivesicular body biogenesis, release of enveloped retroviruses and both reformation of the nuclear envelope and cytokinetic abscission during mitotic exit. These events share the requirement for a topologically equivalent membrane remodeling for their completion and the cells deployment of the ESCRT machinery in these different contexts highlights its functionality as a transposable membrane-fission machinery. Here, we will examine recent data describing ESCRT-III dependent membrane remodeling and explore new roles for the ESCRT-III complex at the nuclear envelope.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Sites and models of ESCRT-III activity. (a) Cartoon depicting sites of topologically-equivalent membrane remodeling performed by the ESCRT-III complex. In all cases, ESCRT-III provides an activity allowing resolution of the membranous stalk with the concomitant separation of the two membranes previously connected by the stalk. This separation achieves release of ILVs (1), enveloped viruses such as HIV-1 (2), daughter cells (3) and separation of previously connected inner and outer nuclear membranes (4). Bottom schematic depicts membrane separation in each case achieved through ESCRT-III activity. (b) Models for ESCRT-III driven membrane fission. Filaments of polymerised ESCRT-III subunits are thought to assemble inside a membranous stalk, connecting two parental membranes. ESCRT-III assembly, either via the shape of the formed holo-polymer (dome model), or through constriction of the ESCRT-III filament (purse string model), narrows the stalk. This narrowing presumably makes it energetically more favourable to separate the membranes, rather than persist with membranes connected by a highly-curved, thin, membranous stalk. Models propose that the AAA-ATPase VPS4 acts either to tighten the filament, through sequential extraction of polymerised CHMPs (purse string model, VPS4 activity needed throughout remodeling event (1)) or through the induction of conformational changes in the CHMPs by direct interaction. Alternatively, membrane fission is accomplished through formation of the ESCRT-III holo-polymer (dome model, with VPS4 acting after fission to disassemble ESCRT-III filaments for subsequent rounds of assembly (2)). Period of VPS4 activity indicated by arrow.
Figure 2
Figure 2
Energetic considerations in ESCRT-III assembly. Cartoon depicting the energy stored in helical polymers of ESCRT-III subunits and the suggestion that this energy is released to allow membrane deformation.
Figure 3
Figure 3
Mitotic ESCRT-III localization. Immunofluorescence analysis of HeLa cells stained with antibodies against endogenous CHMP2A or tubulin as indicated, demonstrating CHMP2A localization to the reforming nuclear envelope (a) or the midbody during cytokinesis (b). For methods and more detailed images, see Olmos et al. (2015). In A, dotted outline depicts cell border, images obtained by deconvolution of widefield images (a) or confocal imaging (b). Scale bar is 10 μm.
Figure 4
Figure 4
Mitotic co-ordination of membrane and cytoskeletal remodeling by ESCRT-III. A. Cartoon depicting similarities between ESCRT-III dependent nuclear envelope reformation (a) and cytokinesis (b). Enlargement of green-boxed region given in lower cartoon. In both cases, prior to ESCRT-III-dependent membrane resolution, microtubules must be coordinately removed through the action of the AAA-ATPase Spastin, which is recruited to the site of remodeling through interaction with IST1 during nuclear envelope reformation, or IST1/CHMP1B during cytokinesis. In the case of cytokinesis, abscission occurs at a constriction upon the midbody arms and whilst cuts can occur on both sides of the Flemming body, here a single cut is depicted with the asymmetric resorption of the Flemming body by one daughter cell as a midbody remnant.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. 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. 2001;106:145–155. - PubMed
    1. 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. 2002;3:283–289. - PubMed
    1. 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. 2002;3:271–282. - PubMed
    1. Wollert T., Wunder C., Lippincott-Schwartz J., Hurley J.H. Membrane scission by the ESCRT-III complex. Nature. 2009;458:172–177. - PMC - PubMed

    2. These papers provided the first demonstration that in vitro reconstitution of ESCRT-III could perform the topologically unique membrane scission ascribed to this complex.

    1. Wollert T., Hurley J.H. Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature. 2010;464:864–869. - PMC - PubMed

    2. These papers provided the first demonstration that in vitro reconstitution of ESCRT-III could perform the topologically unique membrane scission ascribed to this complex.

Publication types

MeSH terms

Substances

LinkOut - more resources