Abstract
SummaryShallow hydrophobic insertions and crescent-shaped BAR scaffolds promote membrane curvature. Here, we investigate membrane fission by shallow hydrophobic insertions quantitatively and mechanistically. We provide evidence that membrane insertion of the ENTH domain of epsin leads to liposome vesiculation, and that epsin is required for clathrin-coated vesicle budding in cells. We also show that BAR-domain scaffolds from endophilin, amphiphysin, GRAF, and β2-centaurin limit membrane fission driven by hydrophobic insertions. A quantitative assay for vesiculation reveals an antagonistic relationship between amphipathic helices and scaffolds of N-BAR domains in fission. The extent of vesiculation by these proteins and vesicle size depend on the number and length of amphipathic helices per BAR domain, in accord with theoretical considerations. This fission mechanism gives a new framework for understanding membrane scission in the absence of mechanoenzymes such as dynamin and suggests how Arf and Sar proteins work in vesicle scission.
Highlights
All eukaryotic cells rely on intracellular compartmentalization of vital processes within membrane organelles, whose shapes and dynamic interplay are tightly regulated to support their functions (Antonny, 2006; McMahon and Gallop, 2005; Shibata et al, 2009)
Several hypothetical models of membrane division have been suggested for Arf1 and dynamin (Beck et al, 2011; Roux et al, 2006; Schmid and Frolov, 2011) and for ESCRTIII (Hurley and Hanson, 2010), but these do not provide a quantitative basis on the forces driving membrane scission
To foresee the effect of shallow hydrophobic insertions and/or crescent-like protein scaffolds on membrane fission, we undertook a comparative analysis of system energies in tubular and vesicular states based on a coarse-grained semiquantitative physical model
Summary
All eukaryotic cells rely on intracellular compartmentalization of vital processes within membrane organelles, whose shapes and dynamic interplay are tightly regulated to support their functions (Antonny, 2006; McMahon and Gallop, 2005; Shibata et al, 2009). Basic cellular compartments, including the endoplasmic reticulum (ER), the Golgi complex (GC), mitochondria, and intracellular transport intermediates (such as endocytic vesicles), contain in their structures highly curved tubular and spherical membrane elements undergoing persistent transformations and mutual conversion (McMahon and Gallop, 2005; Shibata et al, 2009) To form these intracellular membrane shapes, there are two essentially different types of membrane-sculpting events: generation of membrane curvature without disturbing membrane integrity and membrane remodeling by fission and fusion. Several hypothetical models of membrane division have been suggested for Arf and dynamin (Beck et al, 2011; Roux et al, 2006; Schmid and Frolov, 2011) and for ESCRTIII (Hurley and Hanson, 2010), but these do not provide a quantitative basis on the forces driving membrane scission
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