Reverse-topology membrane scission by the ESCRT proteins

Schöneberg, Johannes; Lee, Il‐Hyung; Iwasa, Janet; Hurley, James H.

doi:10.1038/nrm.2016.121

Cited by 352 publications

(399 citation statements)

References 110 publications

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“…[1] Concerning the dome model, we realized that a previous quantitative study of the model [15] contained a computational error which led to wrong predictions for this model, both qualitatively as well as quantitatively. We showed that the neck closure transition for dome-shaped assemblies, which had been incorrectly predicted to be discontinuous, is in fact continuous.…”

Section: Resultsmentioning

confidence: 99%

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Domes and cones: Adhesion-induced fission of membranes by ESCRT proteins

Agudo-Canalejo

Lipowsky

2018

PLoS Comput Biol

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ESCRT proteins participate in the fission step of exocytic membrane budding, by assisting in the closure and scission of the membrane neck that connects the nascent bud to the plasma membrane. However, the precise mechanism by which the proteins achieve this so-called reverse-topology membrane scission remains to be elucidated. One mechanism is described by the dome model, which postulates that ESCRT-III proteins assemble in the shape of a hemispherical dome at the location of the neck, and guide the closure of this neck via membrane–protein adhesion. A different mechanism is described by the flattening cone model, in which the ESCRT-III complex first assembles at the neck in the shape of a cone, which then flattens leading to neck closure. Here, we use the theoretical framework of curvature elasticity and membrane–protein adhesion to quantitatively describe and compare both mechanisms. This comparison shows that the minimal adhesive strength of the membrane–protein interactions required for scission is much lower for cones than for domes, and that the geometric constraints on the shape of the assembly required to induce scission are more stringent for domes than for cones. Finally, we compute for the first time the adhesion-induced constriction forces exerted by the ESCRT assemblies onto the membrane necks. These forces are higher for cones and of the order of 100 pN.

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Section: Resultsmentioning

confidence: 99%

“…[1] Furthermore, in the dome model the complex grows forming a hemispherical shape of fixed radius R do ≃ 25 nm, [15] whereas in the cone model the complex forms a conical shape with flattens as it grows.…”

Section: Discussionmentioning

confidence: 99%

Domes and cones: Adhesion-induced fission of membranes by ESCRT proteins

Agudo-Canalejo

Lipowsky

2018

PLoS Comput Biol

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“…The biogenesis and release of Exos is a complex symphony involving a series of factors, representatively including the endosomal sorting complexes required for transport (ESCRT), ALIX (also known as programed cell death 6‐interacting protein), phospholipase, vacuolar protein sorting‐associated 4 (VPS4), Rab GTPase proteins, sphingomyelinase, and ceramide 57, 58, 59…”

Section: Biogenesis and Release Of Evsmentioning

confidence: 99%

“…The classic mechanism involves a reverse‐topology membrane scission event mediated by an ESCRT‐dependent mechanism 59. The ESCRT machinery, which is formed by four ESCRT proteins (ESCRT‐0, ESCRT‐I, ESCRT‐II, and ESCRT‐III) and accessory proteins including ALIX and VPS4, assemble components of Exos together by forming intraluminal vesicles 60.…”

Section: Biogenesis and Release Of Evsmentioning

confidence: 99%

“…The VPS28 subunit of ESCRT‐I and the VPS36 subunit of ESCRT‐II participate in the connection of the two complexes 66, 67, 68. ESCRT‐III directly participates in remodeling and abscission of the membranes; ultimately, VPS4, the recycling machine, extracts ESCRT‐III monomers from the assembly to recycle the ESCRT‐III subunits 59. An ESCRT‐independent mechanism involves the ceramide‐triggered budding of Exos into MVBs, which is preferentially dependent on certain cargoes 69.…”

Section: Biogenesis and Release Of Evsmentioning

confidence: 99%

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Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation. However, as research has progressed, it is realized that EVs derived from native‐source cells may have various shortcomings, which can be corrected by modification and optimization. To date, attempts are made to modify or improve almost all the components of EVs, including the lipid bilayer, proteins, and nucleic acids, launching a new era of modularized EV therapy through the “modular design” of EV components. One high‐yield technique, generating EV mimetic nanovesicles, will help to make industrial production of modularized EVs a reality. These modularized EVs have highly customized “modular design” components related to biological function and targeted delivery and are proposed as a promising approach to achieve personalized and precision medicine.

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