Mechanisms of membrane deformation
Introduction
Cellular compartmentalisation requires membrane-bound structures. Traffic between membranous organelles occurs via tubular and vesicular membrane carriers that bud and fuse, effectively maintaining the compartmentalised state while allowing for dynamic flux. Over the past few years, we have garnered greater understanding of the molecular processes by which the trafficking organelles — tubules and vesicles — form and behave. Generation of these structures can be driven by a cooperation of mechanisms both extrinsic and intrinsic to the membrane. Mechanical forces applied to the membrane by the cytoskeleton can induce membrane tubule formation. Proteinaceous coats selectively associated with the surface of membrane buds are key mediators of vesicle formation in the endocytic and secretory pathways. Accessory factors to the main constituents of coat proteins have also recently been found to be an integral part of both vesicle formation and cargo selection within the bud. Proteins that can deform the membrane into tubules have been identified and characterised. In addition, lipid components of the membrane, either directly or via interaction with proteins, have been suggested to facilitate the structural changes necessary to deform membranes.
In this review, we will primarily focus on recently described mechanisms for membrane deformation that have expanded our understanding of this process.
Section snippets
Extrinsic forces on the membrane
Cytoskeletal elements have long been known to play some role in membrane traffic, not only by forming the structural scaffold and network over which membrane traffic flows, but also by directly deforming membranes (Figure 1) 1., 2., 3.. A characteristic property of membrane bilayers is that the application of an external focal force results in bilayer tubule formation, rather than a broad ‘tenting’ of the membrane. Many intracellular membrane tubules are generated in this fashion 4.•, 5., 6., 7.
Protein-mediated effects
Over the past few years, emerging data have implicated cytosolic proteins in bilayer deformation upon recruitment to the membrane. Oligomerisation of these proteins into a coat scaffold on the membrane has traditionally been thought to promote budding by imposing curvature on the membrane 18., 19., 20. (Figure 2a). This view, first developed for the clathrin coat, was then extended to other protein coats observed on vesicles, such as COPI [20] and COPII [21], and has since been supported by
Amphipathic peptides and the bilayer-couple hypothesis
The bilayer-couple hypothesis, initially popularised by Sheetz and Singer in 1974, postulates that the two halves of a closed lipid bilayer, by virtue of asymmetries between the bilayer leaflets, could have differential responses to various perturbations 84., 85.. Thus, a relative increase in surface area of one leaflet of a closed bilayer, as discussed above, is predicted to increase the spontaneous curvature of the bilayer. To minimise its energy state and maintain hydrophobic and van der
Conclusions and future directions
Our understanding of the mechanisms generating membrane deformation will no doubt increase our awareness of how this process affects various aspects of cell biology. Roles for membrane budding and tubulation have been described in both immunity and disease. For example, ‘reverse’ budding — budding away from the cytosol — is a mechanism for the formation of the multivesicular bodies (MVBs) in the late endosomal pathway 98., 99., 100.. Recent work in this field has demonstrated a role for three
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
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of special interest
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of outstanding interest
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2020, iScienceCitation Excerpt :Although curvature generation and sensing have been proposed as behaviors by the same proteins at different concentration regimes (Simunovic et al., 2018; Suetsugu and Gautreau, 2012), whether proteins generating curvature are by default curvature sensors remains unknown (Madsen et al., 2010). The BAR (Bin/Amphiphysin/Rvs) domain-containing superfamily proteins share banana-shaped BAR domains that can bind to membrane via their concave faces (Farsad and De Camilli, 2003; Kozlov et al., 2014; McMahon and Gallop, 2005). Because of their shapes (Frost et al., 2009), they are intuitively assumed as both curvature generators and sensors.