Vesicle fusion

Vesicle fusion is the merging of a vesicle with other vesicles or a part of a cell membrane. In the latter case, it is the end stage of secretion from secretory vesicles, where their contents are expelled from the cell through exocytosis. Vesicles can also fuse with other target cell compartments, such as a lysosome. Exocytosis occurs when secretory vesicles transiently dock and fuse at the base of cup-shaped structures at the cell plasma membrane called porosome, the universal secretory machinery in cells. Vesicle fusion may depend on SNARE proteins in the presence of increased intracellular calcium (Ca2+) concentration. Vesicle fusion is the merging of a vesicle with other vesicles or a part of a cell membrane. In the latter case, it is the end stage of secretion from secretory vesicles, where their contents are expelled from the cell through exocytosis. Vesicles can also fuse with other target cell compartments, such as a lysosome. Exocytosis occurs when secretory vesicles transiently dock and fuse at the base of cup-shaped structures at the cell plasma membrane called porosome, the universal secretory machinery in cells. Vesicle fusion may depend on SNARE proteins in the presence of increased intracellular calcium (Ca2+) concentration. Stimuli that trigger vesicle fusion act by increasing intracellular Ca2+. Model systems consisting of a single phospholipid or a mixture have been studied by physical chemists. Cardiolipin is found mainly in mitochondrial membranes, and calcium ions play an important role in the respiratory processes mediated by the mitochondrion. The forces involved have been postulated to explain this process in terms of nucleation for agglomeration of smaller supramolecular entities or phase changes in the structure of the biomembranes. In synaptic vesicle fusion, the vesicle must be within a few nanometers of the target membrane for the fusion process to begin. This closeness allows the cell membrane and the vesicle to exchange lipids which is mediated by certain proteins which remove water that comes between the forming junction. Once the vesicle is in position it must wait until Ca2+ enters the cell by the propagation of an action potential to the presynaptic membrane. Ca2+ binds to specific proteins, one of which is Synaptotagmin, in neurons which triggers the complete fusion of the vesicle with the target membrane. SNARE proteins are also thought to help mediate which membrane is the target of which vesicle. Assembly of the SNAREs into the 'trans' complexes likely bridges the opposing lipid bilayers of membranes belonging to cell and secretory granule, bringing them in proximity and inducing their fusion. The influx of calcium into the cell triggers the completion of the assembly reaction, which is mediated by an interaction between the putative calcium sensor, synaptotagmin, with membrane lipids and/or the partially assembled SNARE complex. One hypothesis implicates the molecule Complexin within the SNARE complex and its interaction with the molecule synaptotagmin. Known as the 'clamp' hypothesis, the presence of complexin normally inhibits the fusion of the vesicle to the cell membrane. However, binding of calcium ions to synaptotagmin triggers the complexin to be released or inactivated, so that the vesicle is then free to fuse.