The mystery of membrane organization: composition, regulation and roles of lipid rafts

Sezgin, Erdinç; Levental, Ilya; Mayor, Satyajit; Eggeling, Christian

doi:10.1038/nrm.2017.16

Cited by 1,654 publications

(1,850 citation statements)

References 193 publications

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“…Membrane rafts, which are highly dynamic membrane domains enriched in sphingolipids and cholesterol that mediate the compartmentalization of signaling proteins and receptors (Lingwood & Simons, 2010; Sezgin et al , 2017), have been shown to be utilized by numerous bacterial pathogens (reviewed in Refs: Lafont & van der Goot, 2005; Bagam et al , 2017). For example, Shigella uses its IpaB effector protein to bind the host raft‐associated CD44 transmembrane receptor (Lafont et al , 2002); entry of Listeria monocytogenes into host cells requires the localization of the host receptors E‐cadherin and HGF‐R/Met in specific lipid domains (Seveau et al , 2004).…”

Section: Introductionmentioning

confidence: 99%

Stress‐induced host membrane remodeling protects from infection by non‐motile bacterial pathogens

et al. 2018

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While mucosal inflammation is a major source of stress during enteropathogen infection, it remains to be fully elucidated how the host benefits from this environment to clear the pathogen. Here, we show that host stress induced by different stimuli mimicking inflammatory conditions strongly reduces the binding of Shigella flexneri to epithelial cells. Mechanistically, stress activates acid sphingomyelinase leading to host membrane remodeling. Consequently, knockdown or pharmacological inhibition of the acid sphingomyelinase blunts the stress‐dependent inhibition of Shigella binding to host cells. Interestingly, stress caused by intracellular Shigella replication also results in remodeling of the host cell membrane, in vitro and in vivo, which precludes re‐infection by this and other non‐motile pathogens. In contrast, Salmonella Typhimurium overcomes the shortage of permissive entry sites by gathering effectively at the remaining platforms through its flagellar motility. Overall, our findings reveal host membrane remodeling as a novel stress‐responsive cell‐autonomous defense mechanism that protects epithelial cells from infection by non‐motile bacterial pathogens.

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Section: Introductionmentioning

confidence: 99%

Stress‐induced host membrane remodeling protects from infection by non‐motile bacterial pathogens

et al. 2018

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“…Over the past two decades, it has become widely accepted that biological membranes are not simply homogeneous seas of lipids studded with proteins, but contain microdomains that play crucial roles in the assembly of signalling platforms and in intracellular transport between various compartments ( Lingwood & Simons, 2010). Although the physical forces that govern membrane microdomains are still poorly understood, it is now commonly accepted that the degree of order in the lipids is highly relevant to the formation of lipid domains in eukaryotic cell membranes ( Rosetti et al , 2017; Sezgin et al , 2017). …”

Section: Introductionmentioning

confidence: 99%

Using spectral decomposition of the signals from laurdan-derived probes to evaluate the physical state of membranes in live cells

2017

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Background: We wanted to investigate the physical state of biological membranes in live cells under the most physiological conditions possible. Methods: For this we have been using laurdan, C-laurdan or M-laurdan to label a variety of cells, and a biphoton microscope equipped with both a thermostatic chamber and a spectral analyser. We also used a flow cytometer to quantify the 450/530 nm ratio of fluorescence emissions by whole cells. Results: We find that using all the information provided by spectral analysis to perform spectral decomposition dramatically improves the imaging resolution compared to using just two channels, as commonly used to calculate generalized polarisation (GP). Coupled to a new plugin called Fraction Mapper, developed to represent the fraction of light intensity in the first component in a stack of two images, we obtain very clear pictures of both the intra-cellular distribution of the probes, and the polarity of the cellular environments where the lipid probes are localised. Our results lead us to conclude that, in live cells kept at 37°C, laurdan, and M-laurdan to a lesser extent, have a strong tendency to accumulate in the very apolar environment of intra-cytoplasmic lipid droplets, but label the plasma membrane (PM) of mammalian cells ineffectively. On the other hand, C-laurdan labels the PM very quickly and effectively, and does not detectably accumulate in lipid droplets. Conclusions: From using these probes on a variety of mammalian cell lines, as well as on cells from Drosophila and Dictyostelium discoideum, we conclude that, apart from the lipid droplets, which are very apolar, probes in intracellular membranes reveal a relatively polar and hydrated environment, suggesting a very marked dominance of liquid disordered states. PMs, on the other hand, are much more apolar, suggesting a strong dominance of liquid ordered state, which fits with their high sterol contents.

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“…In addition to the asymmetry of phospholipid distribution in their membranes, human cells also present planar ordered domains composed of sphingomyelin and cholesterol (lipid rafts) that are important for the membrane proteins and for elastic control of the membrane (Quinn 2010;Rosetti et al 2017;Sezgin et al 2017). Evidence has been gathered indicating that the presence and integrity of lipid rafts is necessary to maintain PS exposure (Ishii et al 2005).…”

Section: The Effect Of Lipid Composition On Affinity and Lytic Activimentioning

confidence: 99%

Lipid-packing perturbation of model membranes by pH-responsive antimicrobial peptides

2017

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The indiscriminate use of conventional antibiotics is leading to an increase in the number of resistant bacterial strains, motivating the search for new compounds to overcome this challenging problem. Antimicrobial peptides, acting only in the lipid phase of membranes without requiring specific membrane receptors as do conventional antibiotics, have shown great potential as possible substituents of these drugs. These peptides are in general rich in basic and hydrophobic residues forming an amphipathic structure when in contact with membranes. The outer leaflet of the prokaryotic cell membrane is rich in anionic lipids, while the surface of the eukaryotic cell is zwitterionic. Due to their positive net charge, many of these peptides are selective to the prokaryotic membrane. Notwithstanding this preference for anionic membranes, some of them can also act on neutral ones, hampering their therapeutic use. In addition to the electrostatic interaction driving peptide adsorption by the membrane, the ability of the peptide to perturb lipid packing is of paramount importance in their capacity to induce cell lysis, which is strongly dependent on electrostatic and hydrophobic interactions. In the present research, we revised the adsorption of antimicrobial peptides by model membranes as well as the perturbation that they induce in lipid packing. In particular, we focused on some peptides that have simultaneously acidic and basic residues. The net charges of these peptides are modulated by pH changes and the lipid composition of model membranes. We discuss the experimental approaches used to explore these aspects of lipid membranes using lipid vesicles and lipid monolayer as model membranes.

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The mystery of membrane organization: composition, regulation and roles of lipid rafts

Cited by 1,654 publications

References 193 publications

Stress‐induced host membrane remodeling protects from infection by non‐motile bacterial pathogens

Stress‐induced host membrane remodeling protects from infection by non‐motile bacterial pathogens

Using spectral decomposition of the signals from laurdan-derived probes to evaluate the physical state of membranes in live cells

Lipid-packing perturbation of model membranes by pH-responsive antimicrobial peptides

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