The 3-Hydroxy Group and 4,5-trans Double Bond of Sphingomyelin Are Essential for Modulation of Galactosylceramide Transmembrane Asymmetry

Malewicz, Barbara; Valiyaveettil, Jacob; Jacob, Kochurani; Byun, Hoe‐Sup; Mattjus, Peter; Baumann, Wolfgang J.; Bittman, Robert; Brown, Rhoderick E.

doi:10.1529/biophysj.104.057059

Cited by 23 publications

(8 citation statements)

References 76 publications

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“…GalCer, at concentrations below 30 mole%, is miscible in both liquid-crystalline and gel-phase SM [35], whereas GalCer mixing in PC becomes less favorable with increasing unsaturation of the fatty acyl chains in PC. NMR studies of GalCer transbilayer distributions in PCs and SMs suggest preferential lateral interactions between GalCer and SM [36,37]. Interestingly, the GLTP-mediated transfer of AV-GalCer seems to be affected by its miscibility state in bilayer membranes composed of SM and PC.…”

Section: Sphingomyelin Phosphatidylcholine and Cholesterol Effects Omentioning

confidence: 98%

Glycolipid transfer proteins

Brown

Mattjus

2007

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Glycolipid transfer proteins (GLTPs) are small (24 kD), soluble, ubiquitous proteins characterized by their ability to accelerate the intermembrane transfer of glycolipids in vitro. GLTP specificity encompasses both sphingoid-and glycerol-based glycolipids, but with a strict requirement that the initial sugar residue be beta-linked to the hydrophobic lipid backbone. The 3D protein structures of GLTP reveal liganded structures with unique lipid binding modes. The biochemical properties of GLTP action at the membrane surface have been studied rather comprehensively, but the biological role of GLTP remains enigmatic. What is clear is that GLTP differs distinctly from other known glycolipid-binding proteins, such as nonspecific lipid transfer proteins, lysosomal sphingolipid activator proteins, lectins, lung surfactant proteins as well as other lipid binding/transfer proteins. Based on the unique conformational architecture that targets GLTP to membranes and enables glycolipid binding, GLTP is now considered the prototypical and founding member of a new protein superfamily in eukaryotes.

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Section: Sphingomyelin Phosphatidylcholine and Cholesterol Effects Omentioning

confidence: 98%

Glycolipid transfer proteins

Brown

Mattjus

2007

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Increasing efforts are being made to prepare asymmetric model membranes (7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and use them to investigate ordered domain formation. Recent studies revealed that in asymmetric planar bilayers mimicking the lipid asymmetry of the plasma membrane, the formation of ordered domains in one leaflet can induce the occurrence of ordered domains in the other leaflet (10).…”

Section: Introductionmentioning

confidence: 99%

Preparation and Properties of Asymmetric Large Unilamellar Vesicles: Interleaflet Coupling in Asymmetric Vesicles Is Dependent on Temperature but Not Curvature

Cheng

London

2011

Biophysical Journal

100

140

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Asymmetry of inner and outer leaflet lipid composition is an important characteristic of eukaryotic plasma membranes. We previously described a technique in which methyl-β-cyclodextrin-induced lipid exchange is used to prepare biological membrane-like asymmetric small unilamellar vesicles (SUVs). Here, to mimic plasma membranes more closely, we used a lipid-exchange-based method to prepare asymmetric large unilamellar vesicles (LUVs), which have less membrane curvature than SUVs. Asymmetric LUVs in which sphingomyelin (SM) or SM + 1-palmitoyl-2-oleoyl-phosphatidylcholine was exchanged into the outer leaflet of vesicles composed of 1,2-dioleoyl-phosphatidylethanolamine (DOPE) and 1-palmitoyl-2-oleoyl-phosphatidylserine (POPS) were prepared with or without cholesterol. Approximately 80-100% replacement of outer leaflet DOPE and POPS was achieved. At room temperature, SM exchange into the outer leaflet increased the inner leaflet lipid order, suggesting significant interleaflet interaction. However, the SM-rich outer leaflet formed an ordered state, melting with a midpoint at ∼37°C. This was about the same value observed in pure SM vesicles, and was significantly higher than that observed in symmetric vesicles with the same SM content, which melted at ∼20°C. In other words, ordered state formation by outer-leaflet SM in asymmetric vesicles was not destabilized by an inner leaflet composed of DOPE and POPS. These properties suggest that the coupling between the physical states of the outer and inner leaflets in these asymmetric LUVs becomes very weak as the temperature approaches 37°C. Overall, the properties of asymmetric LUVs were very similar to those previously observed in asymmetric SUVs, indicating that they do not arise from the high membrane curvature of asymmetric SUVs.

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“…Ordinary vesicle preparation procedures (e.g. sonication) can yield some degree of asymmetry in some cases (34,35), but it can be hard to control. Using pH gradients, asymmetry of small amounts of anionic lipids has been achieved (36,37).…”

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confidence: 99%

Preparation and Properties of Asymmetric Vesicles That Mimic Cell Membranes

Cheng

Megha

London

2009

Journal of Biological Chemistry

183

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A methyl-␤-cyclodextrin-induced lipid exchange technique was devised to prepare small unilamellar vesicles with stable asymmetric lipid compositions. Asymmetric vesicles that mimic biological membranes were prepared with sphingomyelin (SM) or SM mixed with 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) as the predominant lipids in the outer leaflet and dioleoylphosphatidylcholine (DOPC), POPC, 1-palmitoyl-2-oleoyl-phosphatidyl-L-serine (POPS), or POPS mixed with 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) in the inner leaflet. Fluorescence-based assays were developed to confirm lipid asymmetry. Cholesterol was introduced into these vesicles using a second methyl-␤-cyclodextrin exchange step. In asymmetric vesicles composed of SM outside, DOPC inside (SMo/ DOPCi) or SM outside, 2:1 mol:mol POPE:POPS inside (SMo/ 2:1 POPE:POPSi) the outer leaflet SM formed an ordered state with a thermal stability similar to that in pure SM vesicles and significantly greater than that in symmetric vesicles with the same overall lipid composition. Analogous behavior was observed in vesicles containing cholesterol. This shows that an asymmetric lipid distribution like that in eukaryotic plasma membranes can be conducive to ordered domain (raft) formation. Furthermore asymmetric vesicles containing ϳ25 mol % cholesterol formed ordered domains more thermally stable than those in asymmetric vesicles lacking cholesterol, showing that the crucial ability of cholesterol to stabilize ordered domain formation is likely to contribute to ordered domain formation in cell membranes. Additional studies demonstrated that hydrophobic helix orientation is affected by lipid asymmetry with asymmetry favoring formation of the transmembrane configuration. The ability to form asymmetric vesicles represents an important improvement in model membrane studies and should find many applications in the future.Over the last few decades artificial lipid bilayers of various types have been successfully used as models for biological membranes, yielding many important insights into the architecture of cell membranes. Vesicle dispersions (liposomes) have perhaps been the most useful model membrane system. However, commonly used preparation procedures do not provide control over differences in lipid composition between inner and outer leaflets (lipid asymmetry). This is a troubling limitation because biological membranes are highly asymmetric. In mammalian cells the plasma membrane outer leaflet (exofacial monolayer) is enriched in sphingolipids and phosphatidylcholine (PC), 2 whereas the inner leaflet (cytofacial monolayer) is enriched in phosphatidylethanolamine (PE) and phosphatidylserine (PS) (1).The subject of lipid asymmetry has become all the more important because of its potential role in the structure and function of lipid rafts. Lipid rafts are defined as sphingolipid and sterol-rich lipid domains that exist in the liquid-ordered (Lo) state. Rafts are thought to co-exist in many eukaryotic cell membranes with liquid-disordered (Ld) state domains ...

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The 3-Hydroxy Group and 4,5-trans Double Bond of Sphingomyelin Are Essential for Modulation of Galactosylceramide Transmembrane Asymmetry

Cited by 23 publications

References 76 publications

Glycolipid transfer proteins

Glycolipid transfer proteins

Preparation and Properties of Asymmetric Large Unilamellar Vesicles: Interleaflet Coupling in Asymmetric Vesicles Is Dependent on Temperature but Not Curvature

Preparation and Properties of Asymmetric Vesicles That Mimic Cell Membranes

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