Trends in Biochemical Sciences
ReviewMembrane bending: the power of protein imbalance
Section snippets
Bending of biological membranes
Biological membranes are a complex mixture of various lipid species and protein molecules that are more or less embedded in the lipid bilayer [1]. They are also highly dynamic in terms of their composition, shape, and packing density 2, 3. This dynamic nature of biological membranes is key to their ability to mediate biological reactions inside the cell. For example, formation of transport vesicles in cellular trafficking is a carefully orchestrated multistage process involving accumulation of
ER membrane asymmetry and budding of vesicles from the ER
The ER is a highly extended membrane compartment, which, among other functions, serves as the first relay station in the process of assembly and transport of membrane and soluble secretory proteins. These proteins are subsequently exported from the ER via COPII-coated membrane vesicles, which form through sequential assembly of the COPII coat subunits on the cytosolic side of the ER membrane (Figure 1A) [13]. The COPII coat mediates recruitment of cargo proteins into a budding vesicle via
How asymmetric protein crowding affects membrane bending
The lipid membrane is often described as a 2D fluid: its constituents can undergo lateral thermal motion (diffusion) and the membrane is effectively unstretchable [1]. Similarly, the proteins diffusing around in the membrane and bumping into each other can be regarded as a 2D gas exhibiting 2D pressure. If the protein density is small, the pressure of the protein gas obeys the 2D variant of the ideal gas law, p = NkBT/A, where N is the number of proteins, kB is the Boltzmann constant, T is the
Membrane protein concentration
Biological membranes consist of proteins and lipids at mass ratios roughly 2:1 [1]. Compared to other organelles, the ER membrane has a relatively high protein content [25]. More precise quantitative data on the protein content of the ER membrane is currently not available, but we can draw some comparisons with an outstanding molecular analysis of synaptic vesicles, which has estimated that ∼20% of the synaptic vesicle bilayer is occupied by protein transmembrane domains [26]. Transmembrane
Membrane bending by epsin 1
In clathrin-mediated endocytosis, the clathrin coat polymerizes underneath the plasma membrane, eventually forming clathrin-coated vesicles [41]. Polymerization of clathrin on the surface of synthetic membranes is sufficient to drive membrane deformation into small buds [42]. In vivo, however, a host of other proteins cooperate with clathrin; many of which are also capable of inducing membrane deformation on their own [41]. One such protein is epsin 1, which binds to the plasma membrane lipid
Enrichment of proteins at the sites of membrane bending
In order for the effects of crowding to be significant, the asymmetrically distributed proteins should be sufficiently concentrated at the site of membrane bending, and they should be able to diffuse in the plane of the membrane to exert pressure on the membrane. Strong protein–protein interactions, either lateral or between different layers assembled on the membrane, therefore minimize the crowding effects because they essentially freeze the motion of the crowded proteins (Figure 3A). However,
Crowding effects in other membrane processes
We expect that the effect of protein crowding could influence many membrane processes. One example is sorting of GPI-APs at cellular locations downstream from the ER. At the cell surface, GPI-APs are excluded from clathrin-coated vesicles and are instead endocytosed via tubular structures that form a compartment termed the GPI-AP-enriched endosomal compartment (GEEC) [47], although whether GPI-APs are in fact enriched in this compartment is not known [48]. It has been suggested that
Concluding remarks
Cellular environments are crowded. Molecular crowding has been taken into consideration in some studies of biochemical reactions 24, 63, but it should be equally important in membrane dynamics (Box 4). That molecular crowding can affect membrane bending in vivo was indeed suggested by the genetic analysis of COPII formation in budding yeast, because depletion of asymmetric cargoes that would oppose membrane budding promoted COPII vesicle formation [11]. Reconstitution of protein crowding on
Acknowledgments
We thank Dr Cathy Jackson for comments on the manuscript.
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2016, Trends in Cell BiologyCitation Excerpt :This effectively increases the surface pressure of the LD surface monolayer, and proteins are displaced from the increasingly crowded surface to relieve the surface pressure. This occurs because crowding increases the likelihood of proteins colliding in a way where sufficient energy is transferred to displace a neighbor protein with weaker LD surface association [111]. At the same time, increased concentration of LD proteins on LD surfaces limits available binding sites, thus preventing the displaced proteins from re-binding to LDs.
Membrane bending by protein crowding is affected by protein lateral confinement
2016, Biochimica et Biophysica Acta - BiomembranesCitation Excerpt :Many studies have looked at the contribution of coat and accessory proteins to membrane bending and fission during the process of vesicle formation, and at the influence of membrane lipid composition on these processes [8]. However, one parameter that has been until recently largely neglected in molecular analyses of membrane bending is the protein component of the membrane itself [9,10]. Considering that about 2/3 of total mass of biological membranes can be attributed to membrane proteins, their influence on membrane properties is likely to be far from insignificant [11,12].