Lysolipids reversibly inhibit Ca<sup>2+</sup>‐, GTP‐ and pH‐dependent fusion of biological membranes

Chernomordik, Leonid V.; Vogel, Steven S.; Sokoloff, Alexander; Onaran, Hilal; Leikina, Evgenia; Zimmerberg, Joshua

doi:10.1016/0014-5793(93)81330-3

Cited by 183 publications

(158 citation statements)

References 32 publications

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“…Extents of fusion, seen after 1 h, and initial fusion rates were similar regardless of whether donor and acceptor liposomes contained peptide (VSV/VSV) or whether peptide-containing acceptor liposomes were fused to pure donor liposomes (VSV/pure). (1,2,24,25). Hemifusion is associated with negative curvature of the outer membrane leaflet.…”

Section: A Synthetic Vsv G-protein Tms Drives Liposome-liposomementioning

confidence: 99%

“…Hence, it is disfavored upon integration of lysolipids into the outer leaflet since lysolipids stabilize positive curvature due to their inverted cone shape (24). Accordingly, lysolipids have been established as potent and reversible inhibitors of different types of natural fusion reactions at a step preceding membrane merger (25). Here, we assessed whether VSV Gprotein TMS-peptide-mediated fusion is inhibited by adding LPC micelles to the preformed liposomes.…”

Section: A Synthetic Vsv G-protein Tms Drives Liposome-liposomementioning

confidence: 99%

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Peptide Mimics of the Vesicular Stomatitis Virus G-protein Transmembrane Segment Drive Membrane Fusion in Vitro

Langosch¹,

Brosig²,

Pipkorn³

2001

Journal of Biological Chemistry

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The efficiency of cell-cell fusion mediated by heterologously expressed vesicular stomatitis virus G-protein has previously been shown to be affected by mutating its transmembrane segment. Here, we show that a synthetic peptide modeled after this transmembrane segment drives liposome-liposome fusion. Addition of millimolar Ca 2؉ concentrations strongly potentiated the effect of the peptides suggesting that Ca 2؉ -mediated liposome aggregation supports the activity of the peptide. Peptide-driven fusion was suppressed by lysolipid, an established inhibitor of natural membrane fusion, and involved inner and outer leaflets of the liposomal bilayer. Thus, transmembrane segment peptide-driven liposome fusion exhibits important hallmarks characteristic of natural membrane fusion. Importantly, the mutations previously shown to attenuate the function of full-length G-protein in cell-cell fusion also attenuated the fusogenicity of the peptide, albeit in a less pronounced fashion. Therefore, the function of the peptide mimic is dependent on its primary structure, similar to full-length G-protein. Together, our data suggest that the G-protein transmembrane segment is an autonomous functional domain. We propose that it acts at a late step in membrane fusion elicited by vesicular stomatitis virus.

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Section: A Synthetic Vsv G-protein Tms Drives Liposome-liposomementioning

confidence: 99%

Section: A Synthetic Vsv G-protein Tms Drives Liposome-liposomementioning

confidence: 99%

Peptide Mimics of the Vesicular Stomatitis Virus G-protein Transmembrane Segment Drive Membrane Fusion in Vitro

Langosch¹,

Brosig²,

Pipkorn³

2001

Journal of Biological Chemistry

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“…These phenomena are described by the theory of intrinsic curvature, which states that lipid shape contributes to the spontaneous curvature of the membrane (30). In live cell experiments, degranulation of mast cells was inhibited when the contacting monolayers, i.e., the outer leaflet of the vesicle and the inner leaflet of the plasma membrane, were treated with lysophosphatidylcholine, a micelle-forming lipid (positive intrinsic curvature) (31). In contrast, incubation of isolated chromaffin granules with arachidonic acid (negative intrinsic curvature) promotes fusion (32).…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry imaging of mating Tetrahymena show that changes in cell morphology regulate lipid domain formation

Kurczy

Piehowski

Bell

et al. 2010

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

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Mass spectrometry imaging has been used here to suggest that changes in membrane structure drive lipid domain formation in mating single-cell organisms. Chemical studies of lipid bilayers in both living and model systems have revealed that chemical composition is coupled to localized membrane structure. However, it is not clear if the lipids that compose the membrane actively modify membrane structure or if structural changes cause heterogeneity in the surface chemistry of the lipid bilayer. We report that timeof-flight secondary ion mass spectrometry images of mating Tetrahymena thermophila acquired at various stages during mating demonstrate that lipid domain formation, identified as a decrease in the lamellar lipid phosphatidylcholine, follows rather than precedes structural changes in the membrane. Domains are formed in response to structural changes that occur during cellto-cell conjugation. This observation has wide implications in all membrane processes.lipid domains | membranes | phosphatidylcholine

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“…where the outer membrane leaflets mix to form a stalk structure (32)(33)(34)(35)(36)(37)(38). Biological membrane fusion is presumed to proceed through this state.…”

Section: Effect Of Lysolipid On Membrane Fusion and Involvement Of Inmentioning

confidence: 99%

“…Lysolipids stabilize positive curvature upon integration in the outer leaflet because of their inverted cone geometry (38). Because hemifusion is associated with curvature of the outer leaflet, lysolipids are inhibitory to fusion before membrane merger (37). We investigated whether peptide-mediated fusion involved a hemifusion intermediate, and the ability of the peptides to convert the hemifusion state to complete fusion wherein the inner leaflet lipids of the fusing membranes are also involved.…”

Section: Effect Of Lysolipid On Membrane Fusion and Involvement Of Inmentioning

confidence: 99%

Palmitoylated Peptides from the Cysteine-rich Domain of SNAP-23 Cause Membrane Fusion Depending on Peptide Length, Position of Cysteines, and Extent of Palmitoylation

Bhattaram

Nagaraj

2003

Journal of Biological Chemistry

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Synaptosome-associated proteins SNAP-23/25, members of a family of proteins essential for exocytosis, have a highly conserved central cysteine-rich domain that plays an important role in membrane targeting. More than one cysteine in this domain is modified by palmitic acid through a thioester linkage. In an effort to address the biological significance of acylation of this domain, we have generated synthetic peptides corresponding to the cysteine-rich region of SNAP-23 and covalently modified the cysteines with palmitic acid. The interaction of acylated and nonacylated peptides with lipid vesicles and natural membranes has been investigated. Our results indicate that palmitoylation is essential for membrane association. The palmitoylated peptides were able to fuse both model and natural membranes. The extent of fusion depended on the length of the peptides and the number and positions of covalently linked palmitic acids. Peptide-mediated fusion was suppressed by lysolipid and involved both outer and inner leaflets of the lipid bilayer, which is characteristic of natural membrane fusion. Our results suggest an important role for the cysteine-rich palmitoylated domain of SNAP-23 in promoting membrane fusion in cells.The mixing of specific membrane compartments by the process of fusion is a highly regulated event in eukaryotic cells. The fusion process is exquisitely controlled in a manner that does not disturb the structural and functional identity of organelles (1, 2). Several proteins that are involved at different steps in the transport process, from the formation of a transport vesicle until its fusion with the target membrane, have been identified (3-7). The SNARE 1 proteins play a crucial role in the process of intracellular membrane fusion. For fusion to occur, transport vesicles with distinct v-SNAREs have to pair with cognate t-SNAREs at the appropriate target membrane. Syntaxin and SNAP-23/25 are members of the t-SNARE family of proteins, whereas synaptobrevin/vesicle-associated membrane protein are v-SNARE proteins (3-7).Syntaxin, SNAP-25, and vesicle-associated membrane proteins mediate fusion through the formation of helical bundles that span opposing membranes. Hydrophobic C-terminal domains anchor syntaxin and vesicle-associated membrane proteins to the lipid bilayer of the plasma and vesicle membranes, respectively. The crystal structure of the SNARE complex has identified the regions of SNAP-25 that are involved in binary and ternary interactions (8, 9). SNAP-25 and its non-neuronal homolog, syndet/SNAP-23 (10, 11) possess cysteine residues clustered in a relatively unstructured segment between two helical domains. The cysteine residues in this segment are palmitoylated (12)(13)(14). Mutants of syndet and SNAP-25 lacking cysteines, and therefore not palmitoylated, are localized predominantly in the cytoplasm of transfected cells (15,16). Based on mutagenesis of SNAP-25, a minimal plasma membranetargeting domain composed of residues 85-120 has been identified. This segment has the ability to target...

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Lysolipids reversibly inhibit Ca²⁺‐, GTP‐ and pH‐dependent fusion of biological membranes

Cited by 183 publications

References 32 publications

Peptide Mimics of the Vesicular Stomatitis Virus G-protein Transmembrane Segment Drive Membrane Fusion in Vitro

Peptide Mimics of the Vesicular Stomatitis Virus G-protein Transmembrane Segment Drive Membrane Fusion in Vitro

Mass spectrometry imaging of mating Tetrahymena show that changes in cell morphology regulate lipid domain formation

Palmitoylated Peptides from the Cysteine-rich Domain of SNAP-23 Cause Membrane Fusion Depending on Peptide Length, Position of Cysteines, and Extent of Palmitoylation

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Lysolipids reversibly inhibit Ca2+‐, GTP‐ and pH‐dependent fusion of biological membranes

Cited by 183 publications

References 32 publications

Peptide Mimics of the Vesicular Stomatitis Virus G-protein Transmembrane Segment Drive Membrane Fusion in Vitro

Peptide Mimics of the Vesicular Stomatitis Virus G-protein Transmembrane Segment Drive Membrane Fusion in Vitro

Mass spectrometry imaging of mating Tetrahymena show that changes in cell morphology regulate lipid domain formation

Palmitoylated Peptides from the Cysteine-rich Domain of SNAP-23 Cause Membrane Fusion Depending on Peptide Length, Position of Cysteines, and Extent of Palmitoylation

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Lysolipids reversibly inhibit Ca²⁺‐, GTP‐ and pH‐dependent fusion of biological membranes