Human ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation

Bertin, Aurélie; Franceschi, Nicola De; Mora, E. De la; Maity, Sourav; Alqabandi, Maryam; Miguet, Nolwen; Cicco, Aurélie Di; Roos, Wouter H.; Mangenot, Stéphanie; Weissenhorn, Winfríed; Bassereau, Patricia

doi:10.1038/s41467-020-16368-5

Cited by 88 publications

(85 citation statements)

References 67 publications

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“…Recent in vitro studies of the yeast ESCRT-III proteins Vps2–Vps24–Snf7 50 and their human homologs 58 have also demonstrated positive curvature membrane remodeling activity – the same membrane orientation seen in our structures – despite their well-characterized negative membrane curvature deformation activity in vivo. While the significance of those in vitro observations remains to be fully elucidated, it appears that ESCRT-III assemblies are more versatile than previously realized.…”

Section: Discussionsupporting

confidence: 65%

Membrane constriction and thinning by sequential ESCRT-III polymerization

Nguyen

Talledge

McCullough

et al. 2020

Nat Struct Mol Biol

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The Endosomal Sorting Complexes Required for Transport (ESCRTs) mediate diverse membrane remodeling events. These typically require ESCRT-III proteins to stabilize negatively-curved membranes, although recent work has indicated that certain ESCRT-IIIs also participate in positive-curvature membrane shaping reactions. ESCRT-IIIs polymerize into membrane-binding filaments, but the structural basis for negative versus positive membrane remodeling by these proteins remains poorly understood. To learn how certain ESCRT-IIIs shape positively-curved membranes, we determined structures of human membrane-bound CHMP1B-only, membrane-bound CHMP1B+IST1, and IST1-only filaments by electron cryomicroscopy. Our structures show how CHMP1B first polymerizes into a single-stranded helical filament, shaping membranes into moderate-curvature tubules. Subsequently, IST1 assembles a second strand upon CHMP1B, further constricting the membrane tube and reducing its diameter nearly to the fission point. Each step of constriction, thins the underlying bilayer, lowering the barrier to membrane fission. Our structures reveal how a two-component, sequential polymerization mechanism drives membrane tubulation, constriction, and bilayer thinning.

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Section: Discussionsupporting

confidence: 65%

Membrane constriction and thinning by sequential ESCRT-III polymerization

Nguyen

Talledge

McCullough

et al. 2020

Nat Struct Mol Biol

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“…In membranous nanostructures, however, the membrane is strongly curved and the curvature radii approach the sizes of the membrane building units. Self-assembly of the molecules needs to be considered [21]. It is relevant to theoretically describe such membrane as composed of many constituents and apply the methods of statistical physics.…”

Section: Introductionmentioning

confidence: 99%

Minimizing isotropic and deviatoric membrane energy – An unifying formation mechanism of different cellular membrane nanovesicle types

et al. 2020

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Tiny membrane-enclosed cellular fragments that can mediate interactions between cells and organisms have recently become a subject of increasing attention. In this work the mechanism of formation of cell membrane nanovesicles (CNVs) was studied experimentally and theoretically. CNVs were isolated by centrifugation and washing of blood cells and observed by optical microscopy and scanning electron microscopy. The shape of the biological membrane in the budding process, as observed in phospholipid vesicles, in erythrocytes and in CNVs, was described by an unifying model. Taking the mean curvature h and the curvature deviator d of the membrane surface as the relevant parameters, the shape and the distribution of membrane constituents were determined theoretically by minimization of membrane free energy. Considering these results and previous results on vesiculation of red blood cells it was interpreted that the budding processes may lead to formation of different types of CNVs as regards the compartment (exo/endovesicles), shape (spherical/tubular/torocytic) and composition (enriched/depleted in particular kinds of molecules). It was concluded that the specificity of pinched off nanovesicles derives from the shape of the membrane constituents and not primarily from their chemical identity, which explains evidences on great heterogeneity of isolated extracellular vesicles with respect to composition.

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“…It is also difficult to distinguish membrane repair-dependent and -independent functions of ESCRT-III during cell death. In recent years, studies using cryogenic electron tomography have identified multiple membraneinteraction surfaces for the helical assembly of ESCRT polymers [33,34]. The subcomplex specificity may be determined by residues in the stalk, which is important for cargo sorting [23,35].…”

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confidence: 99%

ESCRT-III-mediated membrane repair in cell death and tumor resistance

2020

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The plasma membrane is made of glycerophospholipids that separate the inner and outer parts of the cell. Under physiological conditions, it acts as a barrier and gatekeeper to protect cells from the environment. In pathological situations, it undergoes structural and functional changes, resulting in cell damage. Indeed, plasma membrane damage caused by various stresses (e.g., hypoxia, nutritional deficiencies, ultraviolet radiation, and chemotherapeutic agents) is one of the hallmarks of cell death. Phosphatidylserine exposure and plasma membrane blebbing usually occurs in apoptotic cells, while necrotic cells lose the integrity of the plasma membrane and thereby release intracellular damage-associated molecular patterns. In contrast, the endosomal sorting complex required for transport-III (ESCRT-III), an evolutionarily conserved protein complex with membrane fission machinery, plays a key role in the repair of damaged plasma membranes in various types of regulated cell death, such as necroptosis, pyroptosis, and ferroptosis. These emerging findings indicate that ESCRT-III is a potential target to overcome drug resistance during tumor therapy.

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Human ESCRT-III polymers assemble on positively curved membranes and induce helical membrane tube formation

Cited by 88 publications

References 67 publications

Membrane constriction and thinning by sequential ESCRT-III polymerization

Membrane constriction and thinning by sequential ESCRT-III polymerization

Minimizing isotropic and deviatoric membrane energy – An unifying formation mechanism of different cellular membrane nanovesicle types

ESCRT-III-mediated membrane repair in cell death and tumor resistance

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