Technical Summary


Introduction Cell-cell fusion is a key event in fertilization and during differentiation of muscle, bone and trophoblast cells, and possibly also in stem-cell plasticity, carcinogenesis and tumor progression (Chen et al. Earlier work on fusion mechanisms has been focused on the earliest stages of the fusion pathways, which bring about the first measurable indications of fusion: lipid mixing and the opening of a narrow fusion pore – an aqueous connection between the membranes (Earp et al. Weissenhorn et al., 2007). At later stages of cell-cell fusion, these initial pores of a few nanometers in diameter expand to pores that are readily detectable by fluorescence microscopy (diameter >~0.2 μm) and finally yield an open lumen of cell-size diameter (~10-15 μm). Little is known about the properties of these larger pores and the mechanisms that underlie the enlargement of cytoplasmic bridges from early fusion pores to syncytia (Gattegno et al. For instance, we still do not know whether this enlargement proceeds spontaneously and, if not, whether it is driven by the cytoskeleton (Podbilewicz and White, 1994; Zheng and Chang, 1991), membrane tension (Knutton, 1980) or another, as-yet unidentified, cell machinery. The role of the actin cytoskeleton in cell-cell fusion has drawn special attention in many recent studies. Syncytium formation,