We study the mechanisms of the fusion of two biological membranes into one, which is one of the most universal processes in cell physiology. Proteins mediate membrane fusion in exocytosis, intracellular trafficking, and enveloped viral infection, via unknown rearrangements of lipid bilayers. To find out the possible role of membrane lipids in the regulation of these processes we have studied diverse fusion processes including Ca++-triggered cortical exocytosis, GTP-gamma-S -triggered mast cell degranulation and GTP-dependent rat liver microsome - microsome fusion. We have found one class of naturally occurring membrane phospholipids - lysolipids - that acts as a potent inhibitor of membrane fusion in all experimental systems studied. Inhibition was reversible, did not correlate with lysis and could not be attributed to any specific chemical moiety of lysolipids. Fusion was arrested at a stage preceding fusion pore formation. Our results reverse the long-held view that lysolipids promote biologically significant fusion and suggest that highly bent """"""""stalk"""""""" intermediates, which favor lipids of the molecular shape opposite to that of lysolipids, are common in disparate fusion processes. Because lysolipids are tightly regulated biological compounds, it is intriguing to speculate that cells control local lysolipid concentrations to regulate fusion processes.
| Zaitseva, E; Chernomordik, L (2012) Fusion stage of dengue virus entry: mechanisms and assays. Microsc Microanal 18 Suppl 2:52-3 |
| Rafikova, Elvira R; Melikov, Kamran; Ramos, Corinne et al. (2009) Transmembrane protein-free membranes fuse into xenopus nuclear envelope and promote assembly of functional pores. J Biol Chem 284:29847-59 |
| Chernomordik, Leonid V; Kozlov, Michael M (2008) Mechanics of membrane fusion. Nat Struct Mol Biol 15:675-83 |
| Sapir, Amir; Avinoam, Ori; Podbilewicz, Benjamin et al. (2008) Viral and developmental cell fusion mechanisms: conservation and divergence. Dev Cell 14:11-21 |
| Sapir, Amir; Choi, Jaebok; Leikina, Evgenia et al. (2007) AFF-1, a FOS-1-regulated fusogen, mediates fusion of the anchor cell in C. elegans. Dev Cell 12:683-98 |
| Zhukovsky, Mikhail A; Markovic, Ingrid; Bailey, Austin L (2007) Influence of calcium on lipid mixing mediated by influenza hemagglutinin. Arch Biochem Biophys 465:101-8 |
| Efrat, Avishay; Chernomordik, Leonid V; Kozlov, Michael M (2007) Point-like protrusion as a prestalk intermediate in membrane fusion pathway. Biophys J 92:L61-3 |
| Gattegno, Tamar; Mittal, Aditya; Valansi, Clari et al. (2007) Genetic control of fusion pore expansion in the epidermis of Caenorhabditis elegans. Mol Biol Cell 18:1153-66 |
| Ramos, Corinne; Rafikova, Elvira R; Melikov, Kamran et al. (2006) Transmembrane proteins are not required for early stages of nuclear envelope assembly. Biochem J 400:393-400 |
| Chernomordik, Leonid V; Melikov, Kamran (2006) Are there too many or too few SNAREs in proteoliposomes? Biophys J 90:2657-8 |
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