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 1,637 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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“…Accordingly, the membrane is not simply a supporting material for ion channels, but an integral counterpart in which chemical and physical features intervene in channel dynamics. 15) In fact, the fluidity and mosaicity of biomembranes, 16,17) involving varying local fluidity, asymmetry of leaflets, 18,19) and the existence of local domains with different chemical compositions and physical phases, 20) complicate channel-membrane interactions. Thus, even though studying the channel in the membrane is prerequisite, biomembranes are too complex a system to study easily and in isolation; an alternative simple system of study is necessary.…”

Section: Introduction: Channel Function In the Cell Membranementioning

confidence: 99%

Lipid Bilayers Manipulated through Monolayer Technologies for Studies of Channel-Membrane Interplay

Oiki

Iwamoto

2018

Biological & Pharmaceutical Bulletin

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Fluidity and mosaicity are two critical features of biomembranes, by which membrane proteins function through chemical and physical interactions within a bilayer. To understand this complex and dynamic system, artificial lipid bilayer membranes have served as unprecedented tools for experimental examination, in which some aspects of biomembrane features have been extracted, and to which various methodologies have been applied. Among the lipid bilayers involving liposomes, planar lipid bilayers and nanodiscs, recent developments of lipid bilayer methods and the results of our channel studies are reviewed herein. Principles and techniques of bilayer formation are summarized, which have been extended to the current techniques, where a bilayer is formed from lipid-coated water-in-oil droplets (water-in-oil bilayer). In our newly developed method, termed the contact bubble bilayer (CBB) method, a water bubble is blown from a pipette into a bulk oil phase, and monolayer-lined bubbles are docked to form a bilayer through manipulation by pipette. An asymmetric bilayer can be readily formed, and changes in composition in one leaflet were possible. Taking advantage of the topological configuration of the CBB, such that the membrane's hydrophobic interior is contiguous with the surrounding bulk organic phase, oil-dissolved substances such as cholesterol were delivered directly to the bilayer interior to perfuse around the membrane-embedded channels (membrane perfusion), and current recordings in the single-channel allowed detection of immediate changes in the channels' response to cholesterol. Chemical and mechanical manipulation in each monolayer (monolayer technology) allows the examination of dynamic channel-membrane interplay.

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

Cited by 1,637 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 Bilayers Manipulated through Monolayer Technologies for Studies of Channel-Membrane Interplay

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