Interaction of Cholesterol with Sphingomyelin in Mixed Membranes Containing Phosphatidylcholine, Studied by Spin-Label ESR and IR Spectroscopies. A Possible Stabilization of Gel-Phase Sphingolipid Domains by Cholesterol

Veiga, M. P.; Arrondo, José Luis R.; Goñi, Félix M.; Alonso, Alicia; Marsh, D.

doi:10.1021/bi0019803

Cited by 142 publications

(131 citation statements)

References 28 publications

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“…Several experimental data indicate a strong tendency of SM and cholesterol to interact with each other, mainly caused by van der Waals attractive forces between the saturated acyl chain of SM and the rigid cholesterol ring backbone (52,54). In addition, experimental and computational data suggest that hydrogen bonds between SM and cholesterol might facilitate their interaction, presumably via the amide group of SM and the 3-hydroxyl of cholesterol (55,56).…”

Section: Ipc-ergosterolmentioning

confidence: 99%

Yeast Lipids Can Phase-separate into Micrometer-scale Membrane Domains

Klose

Ejsing

García‐Sáez

et al. 2010

Journal of Biological Chemistry

100

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The lipid raft concept proposes that biological membranes have the potential to form functional domains based on a selective interaction between sphingolipids and sterols. These domains seem to be involved in signal transduction and vesicular sorting of proteins and lipids. Although there is biochemical evidence for lipid raft-dependent protein and lipid sorting in the yeast Saccharomyces cerevisiae, direct evidence for an interaction between yeast sphingolipids and the yeast sterol ergosterol, resulting in membrane domain formation, is lacking. Here we show that model membranes formed from yeast total lipid extracts possess an inherent self-organization potential resulting in liquid-disordered-liquid-ordered phase coexistence at physiologically relevant temperature. Analyses of lipid extracts from mutants defective in sphingolipid metabolism as well as reconstitution of purified yeast lipids in model membranes of defined composition suggest that membrane domain formation depends on specific interactions between yeast sphingolipids and ergosterol. Taken together, these results provide a mechanistic explanation for lipid raft-dependent lipid and protein sorting in yeast.The membranes that surround the various organelles of eukaryotic cells have distinct lipid compositions. For example, the concentration of sphingolipids and sterols increases along the secretory pathway, being lowest in the endoplasmic reticulum and highest at the plasma membrane (1-3). The major sorting station for vesicular transport of proteins and lipids within the cell is the trans-Golgi network (4). Here, clusters of sphingolipids and sterols as well as proteins have been proposed to be involved in the formation of secretory vesicles (SVs) 3 (5, 6). These clusters, called lipid rafts, were proposed to form by the preferential interaction between lipids containing saturated acyl chains, especially (glyco-) sphingolipids and sterols, and by intermolecular hydrogen bonds between (glyco-) sphingolipids. As compared with bulk cellular membranes, lipid rafts are characterized by a higher acyl chain order and tight packing of lipids (7). Protein-free model membranes have been widely used to study the self-associative properties of sphingolipids and sterols, which are believed to be responsible for lipid raft formation in vivo (8,9). In model membranes with a lipid composition similar to that of detergent-resistant membranes (DRMs) from mammalian cells, the preferential interaction between sphingolipids and sterols is manifested as the coexistence of two fluid membrane phases, which can be observed microscopically in giant unilamellar vesicles (GUVs) (10 -13). More specifically, model membranes produced from equimolar mixtures of sphingomyelin (SM), phosphatidylcholine (PC), and cholesterol show domains in the liquid-disordered (Ld) state that are enriched in PC coexisting with a liquid-ordered (Lo) phase rich in SM and cholesterol, the latter being a defining component of the Lo phase (14, 15). The Lo phase is characterized by a higher acyl chain (...

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Section: Ipc-ergosterolmentioning

confidence: 99%

Yeast Lipids Can Phase-separate into Micrometer-scale Membrane Domains

Klose

Ejsing

García‐Sáez

et al. 2010

Journal of Biological Chemistry

100

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“…The most compelling evidence for lateral diversity in the bilayer is the presence of lipid rafts, currently defined as dynamic, nano-sized, sterolsphingolipid-enriched assemblies in which protein and lipid content fluctuates on a subsecond time scale (2,3). It is clear that in model membrane systems, sphingolipid and cholesterol selfassociate into liquid-ordered (Lo) phases wherein hydrocarbon chains are longer and more saturated, leading to a thicker, more condensed assemblage that segregates away from liquiddisordered (Ld) unsaturated glycerophospholipids (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The challenge of the raft concept relates to how we rationalize these biophysical principles in the context of the compositional complexity of cell membranes.…”

mentioning

confidence: 99%

Plasma membranes are poised for activation of raft phase coalescence at physiological temperature

Lingwood

Ries

Schwille

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

353

336

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In this work we demonstrate that raft clustering, i.e., amplifying underlying raft-based connectivity to a larger scale, makes an analogous capacity accessible at 37°C. In plasma membranes at this temperature, cholera toxin-mediated cross-linking of the raft ganglioside GM1 induced the steroldependent emergence of a slower diffusing micrometer-scale phase that was enriched in cholesterol and selectively reorganized the lateral distribution of membrane proteins. Although parallels can be drawn, we argue that this raft coalescence in a complex biological matrix cannot be explained by only those interactions that define Lo formation in model membranes. Under this light, our induction of raft-phase separation suggests that plasma membrane composition is poised for selective and functional raft clustering at physiologically relevant temperature. cholera toxin ͉ clustering ͉ ganglioside ͉ lateral sorting H eterogeneity is a fundamental feature of biological membranes, especially those of eukaryotes. It has been calculated that the mammalian bilayer could possess up to 9,600 species of glycerophospholipid, Ͼ100,000 species of sphingolipid, thousands of mono/di/triacylglycerol variants, and not to mention numerous fatty acid-and sterol-based structures (1). Combined with an abundance of protein types, this constitutes an enormous compositional complexity that in itself is difficult to conceptualize as a homogeneous milieu. The most compelling evidence for lateral diversity in the bilayer is the presence of lipid rafts, currently defined as dynamic, nano-sized, sterolsphingolipid-enriched assemblies in which protein and lipid content fluctuates on a subsecond time scale (2, 3). It is clear that in model membrane systems, sphingolipid and cholesterol selfassociate into liquid-ordered (Lo) phases wherein hydrocarbon chains are longer and more saturated, leading to a thicker, more condensed assemblage that segregates away from liquiddisordered (Ld) unsaturated glycerophospholipids (4-13). The challenge of the raft concept relates to how we rationalize these biophysical principles in the context of the compositional complexity of cell membranes.Evaluation of raft-based organization in biological membranes has been difficult because of the lack of available tools that can both be successfully applied to living cells and used to measure fluctuating nanoscale heterogeneities reliably (3). Nevertheless, recent advances in a number of biophysical techniques have identified cholesterol-dependent nanoassemblies consistent with the notion of metastable raft entities in a number of cell types (14-17). Furthermore, work by Baumgart et al. (18) has shown that these lateral organizing properties may be revealed at micrometer scales as by induction of phase separation into Lo-like and Ld-like states in cooled formaldehyde-isolated plasma membrane vesicles. Our work concerns the activation of an analogous capacity at 37°C.Raft-based heterogeneity can be visualized by analysis of the activated condition, a situation in which the metastabl...

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“…This idea is supported by theˆnding of SM-and cholesterolrich DRMs in mixtures of TR and vesicles made of PC, SM, and cholesterol (53). SM interacts with cholesterol in bilayers, possibly through hydrogen bonding between the 3b-OH of cholesterol and the carbonyl group of SM (52,56,57). A debate exists around the possibility that the condensation of SM monolayers in the presence of cholesterol indicates a speciˆc interaction between these two lipids.…”

Section: Why Are Drms Not Raftsmentioning

confidence: 99%

“…Others have also suggested that rafts resist solubilization because they exist in the Lo phase. Mixtures of sphingomyelin and cholesterol, two lipids presumably common in rafts, are known to give rise to Lo phases (56). The Lo phase is characterized by translational diŠusion and a high degree of molecular order in the hydrocarbon chains.…”

Section: Why Are Drms Not Raftsmentioning

confidence: 99%

Principles of microdomain formation in biological membranes— Are there lipid liquid ordered domains in living cellular membranes?

Hichem¹,

Konrad²

2008

TIGG

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277Trends in Glycoscience and Glycotechnology Vol. 20 No. 116 (2008) AbstractRecently, there has been considerable controversy surrounding lipid rafts contained in the plasma membrane. It has been suggested that these microdomains enriched in cholesterol and sphingolipids could play an important role in many cellular processes including signal transduction, membrane tra‹cking, cytoskeletal organization, and pathogen entry. However, rafts have proven

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Interaction of Cholesterol with Sphingomyelin in Mixed Membranes Containing Phosphatidylcholine, Studied by Spin-Label ESR and IR Spectroscopies. A Possible Stabilization of Gel-Phase Sphingolipid Domains by Cholesterol

Cited by 142 publications

References 28 publications

Yeast Lipids Can Phase-separate into Micrometer-scale Membrane Domains

Yeast Lipids Can Phase-separate into Micrometer-scale Membrane Domains

Plasma membranes are poised for activation of raft phase coalescence at physiological temperature

Principles of microdomain formation in biological membranes— Are there lipid liquid ordered domains in living cellular membranes?

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