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BAR scaffolds drive membrane fission by crowding disordered domains.

ABSTRACT: Cellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain-containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains often also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain-containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission. Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. These data suggest that the ability to concentrate disordered domains is a key driver of membrane remodeling and fission by BAR domain-containing proteins.

SUBMITTER: Snead WT

PROVIDER: S-EPMC6363457 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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BAR scaffolds drive membrane fission by crowding disordered domains.

Snead Wilton T WT Zeno Wade F WF Kago Grace G Perkins Ryan W RW Richter J Blair JB Zhao Chi C Lafer Eileen M EM Stachowiak Jeanne C JC

The Journal of cell biology 20181130 2

Cellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain-containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains often also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-len ...[more]

PMID: 30504247

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Project description:I-BAR proteins are well-known actin-cytoskeleton adaptors and have been observed to be involved in the formation of plasma membrane protrusions (filopodia). I-BAR proteins contain an all-helical, crescent-shaped IRSp53-MIM domain (IMD) dimer that is believed to be able to couple with a membrane shape. This coupling could involve the sensing and even the generation of negative plasma membrane curvature. Indeed, the in vitro studies have shown that IMDs can induce inward tubulation of liposomes. While N-BAR domains, which generate positive membrane curvature, have received a considerable amount of attention from both theory and experiments, the mechanisms of curvature coupling through IMDs are comparatively less studied and understood. Here we used a membrane-shape stability assay developed recently in our lab to quantitatively characterize IMD-induced membrane-shape transitions. We determined a membrane-shape stability diagram for IMDs that reveals how membrane tension and protein density can comodulate the generation of IMD-induced membrane protrusions. From comparison to analytical theory, we determine three key parameters that characterize the curvature coupling of IMD. We find that the curvature generation capacity of IMDs is significantly stronger compared to that of endophilin, an N-BAR protein known to be involved in plasma membrane shape transitions. Contrary to N-BAR domains, where amphipathic helix insertion is known to promote its membrane curvature generation, for IMDs we find that amphipathic helices inhibit membrane shape transitions, consistent with the inverse curvature that IMDs generate. Importantly, in both of these types of BAR domains, electrostatic interactions affect membrane-binding capacity, but do not appear to affect the curvature generation capacity of the protein. These two types of BAR domain proteins show qualitatively similar membrane shape stability diagrams, suggesting an underlying ubiquitous mechanism by which peripheral proteins regulate membrane curvature.

Dataset Information

BAR scaffolds drive membrane fission by crowding disordered domains.

Publications

BAR scaffolds drive membrane fission by crowding disordered domains.

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