Protein crowding mediates membrane remodeling in upstream ESCRT-induced formation of intraluminal vesicles

As part of the lysosomal degradation pathway, the endosomal sorting complexes required for transport (ESCRT-0 to -III/VPS4) sequester receptors at the endosome and simultaneously deform the membrane to generate intraluminal vesicles (ILVs). Whereas ESCRT-III/VPS4 have an established function in ILV...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-11, Vol.117 (46), p.28614-28624
Main Authors: Liese, Susanne, Wenzel, Eva Maria, Kjos, Ingrid, Molina, Rossana Rojas, Schultz, Sebastian W., Brech, Andreas, Stenmark, Harald, Raiborg, Camilla, Carlson, Andreas
Format: Article
Language:English
Subjects:
Biological Sciences
Cleavage
Crowding
Deformation
Electron microscopy
Endosomal Sorting Complexes Required for Transport - metabolism
Endosomes
Endosomes - metabolism
Endosomes - ultrastructure
HeLa Cells
Humans
Intracellular Membranes - physiology
Lysosomes
Mathematical models
Membrane proteins
Membrane vesicles
Membranes
Models, Biological
Physical Sciences
Rigidity
Upstream
Vesicles
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Summary:As part of the lysosomal degradation pathway, the endosomal sorting complexes required for transport (ESCRT-0 to -III/VPS4) sequester receptors at the endosome and simultaneously deform the membrane to generate intraluminal vesicles (ILVs). Whereas ESCRT-III/VPS4 have an established function in ILV formation, the role of upstream ESCRTs (0 to II) in membrane shape remodeling is not understood. Combining experimental measurements and electron microscopy analysis of ESCRT-III–depleted cells with a mathematical model, we show that upstream ESCRT-induced alteration of the Gaussian bending rigidity and their crowding in concert with the transmembrane cargo on the membrane induce membrane deformation and facilitate ILV formation: Upstream ESCRT-driven budding does not require ATP consumption as only a small energy barrier needs to be overcome. Our model predicts that ESCRTs do not become part of the ILV, but localize with a high density at the membrane neck, where the steep decline in the Gaussian curvature likely triggers ESCRT-III/VPS4 assembly to enable neck constriction and scission.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2014228117