Abstract
BackgroundESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck. It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Distinct from other cytoskeletal filaments, ESCRT-III filaments do not consume energy themselves, but work in conjunction with another ATP-consuming complex. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling.ResultsHere we present a minimal coarse-grained model that captures all the experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of downward and upward cones and tubules. This model suggests that a change in the geometry of membrane bound ESCRT-III filaments—from a flat spiral to a 3D helix—drives membrane deformation. We then show that such repetitive filament geometry transitions can induce the fission of cargo-containing vesicles.ConclusionsOur model provides a general physical mechanism that explains the full range of ESCRT-III-dependent membrane remodelling and scission events observed in cells. This mechanism for filament force production is distinct from the mechanisms described for other cytoskeletal elements discovered so far. The mechanistic principles revealed here suggest new ways of manipulating ESCRT-III-driven processes in cells and could be used to guide the engineering of synthetic membrane-sculpting systems.
Highlights
Cellular membranes require constant remodelling to allow cells to maintain homeostasis, to grow, and to divide
Filament geometry is controlled by bond lengths linking neighbouring triplets (Fig. 1a), while rigidity, measured by filament persistence, is controlled by bond strength between the triplets
Membrane scission To explore whether transitions in filament geometry can drive scission, we introduced a simple generic cargo into the model
Summary
Cellular membranes require constant remodelling to allow cells to maintain homeostasis, to grow, and to divide This involves protein machines that can physically sculpt membranes in both directions, toward and away from the cytoplasm. The ESCRT-III family of proteins (endosomal sorting complexes required for transport III) is the only cellular apparatus known to deform and cut cell membranes protruding away from the cytoplasm. This is a topologically difficult transition, as the membrane needs. ESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
