Endosomal sorting complexes required for transport (ESCRTs) are required for the lysosomal degradation of plasma membrane proteins, budding of most enveloped viruses, cytokinesis and autophagy.
ESCRT-I and ESCRT-II work together to bud membranes away from the cytosol by stabilizing the neck of the bud.
ESCRT-III forms helical assemblies that sever membrane necks from within.
The AAA+ ATPase vacuolar protein sorting 4 (Vps4) forms a dodecameric assembly together with Vta1 that solubilizes and recycles membrane-bound ESCRT-III following membrane scission.
The endosomal sorting complexes required for transport (ESCRTs) catalyse one of the most unusual membrane remodelling events in cell biology. ESCRT-I and ESCRT-II direct membrane budding away from the cytosol by stabilizing bud necks without coating the buds and without being consumed in the buds. ESCRT-III cleaves the bud necks from their cytosolic faces. ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis and, probably, autophagy. Recent studies of ultrastructures induced by ESCRT-III overexpression in cells and the in vitro reconstitution of the budding and scission reactions have led to breakthroughs in understanding these remarkable membrane reactions.
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Research in the Hurley laboratory is supported by the intramural program of the National Institutes of Health, The National Institute of Diabetes and Digestive and Kidney Diseases and the Intramural AIDS Targeted Antiretroviral Program. Research in the Hanson laboratory is supported by grants from the National Institutes of Health and the American Heart Association. Both authors thank the members of their laboratories and other colleagues for helpful discussions.
The authors declare no competing financial interests.
A cellular organelle in metazoa that is primarily responsible for degradation of unneeded or harmful materials and their recycling into biosynthetic precursors.
- AAA+ ATPase
A protein belonging to a family of ATPases associated with diverse cellular activities. Each enzyme contains one or two AAA motifs of 230 to 250 amino acids, including the Walker homology sequences of P-loop ATPases and regions of similarity that are unique to AAA proteins.
Used here to refer to macroautophagy, the process of envelopment of the cytosol and other material by the phagophore, which subsequently fuses with the lysosome.
A synthetic vesicle of 5–50 μm in size that is useful for visualizing membrane deformation by fluorescence microscopy.
A conserved 76 amino acid protein that is covalently attached through its C terminus to Lys residues of many proteins, including proteins trafficked to MVBs by ESCRTs.
- Gag protein
The protein product of the HIV-1 gag gene, consisting of four functional segments: MA, CA, NC and p6. The p6 segment contains the motifs PTAP and YPXL, which bind to ESCRT-I and ALIX, respectively.
A dense protein structure located at the centre of the narrow membrane neck that connects two dividing cells.
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Hurley, J., Hanson, P. Membrane budding and scission by the ESCRT machinery: it's all in the neck. Nat Rev Mol Cell Biol 11, 556–566 (2010). https://doi.org/10.1038/nrm2937
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