Lipid Composition of Rat Liver Plasma Membranes

Ray, Tapas K.; Skipski, Vladimir P.; Barclay, Marion; Essner, Edward; Archibald, F. M.

doi:10.1016/s0021-9258(18)63595-1

Cited by 183 publications

(32 citation statements)

References 38 publications

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“…Specifically, the low [Chol] i values determined by our method ( 19 ) are in disagreement with other reports indicating that [Chol] i is higher than [Chol] o ( 23 , 24 ). Also, our results are apparently at odds with the previous reports indicating that the total cholesterol concentration in the PM is about 40 mol% ( 25 , 26 , 27 ), because the average cholesterol concentration calculated from our [Chol] i and [Chol] o values is ≈22 mol% ( 19 ). In light of growing interest in cholesterol-mediated cell signaling and regulation in health and disease ( 28 , 29 , 30 ), it is imperative that this controversy should be resolved for the cholesterol research community.…”

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confidence: 99%

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Evaluation of the available cholesterol concentration in the inner leaflet of the plasma membrane of mammalian cells

Buwaneka

Ralko

Liu

et al. 2021

Journal of Lipid Research

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Cholesterol is an essential component of the mammalian plasma membrane involved in diverse cellular processes. Our recent quantitative imaging analysis using ratiometric cholesterol sensors showed that the available cholesterol concentration in the inner leaflet of the plasma membrane (IPM) is low in unstimulated cells and increased in a stimulus-specific manner to trigger cell signaling events. However, the transbilayer distribution of cholesterol in the plasma membrane of mammalian cells remains controversial. Here we report a systematic and rigorous evaluation of basal IPM cholesterol levels in a wide range of mammalian cells with different properties employing cholesterol sensors derived from the D4 domain of the Perfringolysin O toxin and a sterol-transfer protein, Osh4. Results consistently showed that, although basal IPM cholesterol levels vary significantly among cells, they remain significantly lower than cholesterol levels in the outer leaflets. We found that IPM cholesterol levels were particularly low in all tested primary cells. These results support the universality of the low basal IPM cholesterol concentration under physiological conditions. We also report here the presence of sequestered IPM cholesterol pools, which may become available to cytosolic proteins under certain physiological conditions. We hypothesize that these pools may partly account for the low basal level of available IPM cholesterol. In conclusion, we provide new experimental data that confirm the asymmetric transbilayer distribution of the plasma membrane cholesterol, which may contribute to regulation of various cellular signaling processes at the plasma membrane.

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confidence: 99%

“…This potential gap between the available and total IPM cholesterol concentration values may partially account for the discrepancy among reported PM cholesterol concentrations determined by different methods (19,(25)(26)(27). It may also provide a partial answer to the question of energetics of transbilayer cholesterol asymmetry at the PM.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the available cholesterol concentration in the inner leaflet of the plasma membrane of mammalian cells

Buwaneka

Ralko

Liu

et al. 2021

Journal of Lipid Research

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“…In mammalian cell membranes the most abundant sterol is cholesterol, whereas in yeast and plant cell membranes it is ergosterol and phytosterol respectively 15 . Cholesterol is typically present at concentrations of 30-40% 16,17 although this may vary across different regions of the membrane, and is higher in sphingolipid enriched areas 18 . Cholesterol has been shown to bind and modulate a broad range of membrane proteins including G-protein coupled receptors (GPCRs), ion channels and solute transporters 6,[19][20][21][22][23] .…”

Section: Introductionmentioning

confidence: 99%

Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations

Ansell

Curran

Horrell

et al. 2021

Preprint

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Specific interactions of lipids with membrane proteins contribute to protein stability and function. Multiple lipid interactions surrounding a membrane protein are often identified in molecular dynamics (MD) simulations and are, increasingly, resolved in cryo-EM densities. Determining the relative importance of specific interaction sites is aided by determination of lipid binding affinities by experimental or simulation methods. Here, we develop a method for determining protein-lipid binding affinities from equilibrium coarse-grained MD simulations using binding saturation curves, designed to mimic experimental protocols. We apply this method to directly obtain affinities for cholesterol binding to multiple sites on a range of membrane proteins and compare our results with free energies obtained from density-based equilibrium methods and with potential of mean force calculations, getting good agreement with respect to the ranking of affinities for different sites. Thus, our binding saturation method provides a robust, high-throughput alternative for determining the relative consequence of individual sites seen in e.g. cryo-EM derived membrane protein structures surrounded by a plethora of ancillary lipid densities.

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“…The phospholipid composition of biological membranes is specific and tightly controlled. The phospholipid content has been catalogued for many different organisms and tissues (Holub et al, 1970;Nozawa et al, 1975;Ray et al, 1969) and comprehensively reviewed by Ansell et al (1973). In experiments of Wieslander et al (1986) Acholeplasma laidlawii were shown to adjust their lipid composition in response to the incorporation of foreign molecules.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Acyl Chain Length and Saturation of Diacylglycerols and Phosphatidylcholines on Membrane Monolayer Curvature

Szule

Fuller

Rand

2002

Biophysical Journal

180

164

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The second messenger, diacylglycerol (DAG), introduces negative curvature in phospholipid monolayers and strongly induces the lamellar (L(alpha)) to reverse hexagonal (H(II)) phase transition. The chain lengths and degree of unsaturation of symmetric DAGs influence this effect. Within dioleoylphosphatidylcholine (DOPC) monolayers, the apparent spontaneous radius of curvature (R(0)) of the short, saturated dicaprylglycerol (C10-DCG) itself was determined to be -13.3 A, compared with an R(0) value of -10.1 A for the long, di-monounsaturated dioleoylglycerol (C18-DOG). Such increased length and unsaturation of the DAG acyl chains produces this small change. Di-saturated phosphatidylcholines (PCs) with equal length chains (from C10-C18) with 25 mol % DOG do not form the H(II) phase, even under the unstressed conditions of excess water and alkane. Di-unsaturated PCs with equal chain length (from C14-C18) with 25 mol % DOG do form the H(II) phase. Asymmetric chained PCs (position 1 saturated with varying lengths, position 2 differentially unsaturated with varying lengths) all form the H(II) phase in the presence of 25 mol % DOG. As a general rule for PCs, their unsaturation is critical for the induction of the H(II) phase by DOG. The degree of curvature stress induced by the second messenger DOG in membranes, and any protein that might be affected by it, would appear to depend on chain unsaturation of neighboring PCs.

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Lipid Composition of Rat Liver Plasma Membranes

Cited by 183 publications

References 38 publications

Evaluation of the available cholesterol concentration in the inner leaflet of the plasma membrane of mammalian cells

Evaluation of the available cholesterol concentration in the inner leaflet of the plasma membrane of mammalian cells

Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations

The Effects of Acyl Chain Length and Saturation of Diacylglycerols and Phosphatidylcholines on Membrane Monolayer Curvature

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