The Role Of The Transmembrane Domain Of Synaptobrevin In Exocytosis
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Exocytosis is a process used by many cells to move material out of the cell. This process is used by nerve cells to communicate with one another at synapses. This communication is achieved in part by the release of neurotransmitters at the nerve terminal into the extracellular space. Neurotransmitters are contained in membrane bound organelles called vesicles. These vesicles dock and fuse with the plasma membrane of the cell, where a fusion pore is created to allow for the diffusion of neurotransmitters into the extracellular space. The study of exocytosis has led to the identification of the SNARE proteins, located on the vesicle (v-SNARE) and on the plasma membrane (t-SNARE). The v-SNARE and the t-SNARE form a tight complex that holds the vesicle close to the cell plasma membrane. However, it is unclear whether the SNARE proteins also participate in the creation the fusion pore. In this thesis, the role of the v-SNARE protein, synaptobrevin-2 is explored, in particular the role of its transmembrane domain which is embedded into the vesicle membrane. It turns out that the formation of the SNARE complex formed by the association of the vSNARE and the t-SNARE pulls the C-terminus of synaptobrevin into the vesicle lipid membrane, and with this movement, it disrupts the membrane continuity leading the formation of the fusion pore. In addition, the transmembrane domain of synaptobrevin-2 is located at the vincinity of the fusion pore during the fusion pore expansion.