Centre for Integrative Physiology, University of Edinburgh Medical School, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
Cell Mol Neurobiol. 2010 Nov;30(8):1321-6. doi: 10.1007/s10571-010-9599-4. Epub 2010 Nov 3.
The SNARE proteins, syntaxin, SNAP-25, and synaptobrevin have long been known to provide the driving force for vesicle fusion in the process of regulated exocytosis. Of particular interest is the initial interaction between SNAP-25 and syntaxin to form the t-SNARE heterodimer, an acceptor for subsequent synaptobrevin engagement. In vitro studies have revealed at least two different dynamic conformations of t-SNARE heterodimer defined by the degree of association of the C-terminal SNARE motif of SNAP-25 with syntaxin. At the plasma membrane, these proteins are organized into dense clusters of 50-60 nm in diameter. More recently, the t-SNARE interaction within these clusters was investigated in live cells at the molecular level, estimating each cluster to contain 35-70 t-SNARE molecules. This work reported the presence of both partially and fully zippered t-SNARE complex at the plasma membrane in agreement with the earlier in vitro findings. It also revealed a spatial segregation into distinct clusters containing predominantly one conformation apparently patterned by the surrounding lipid environment. The reason for this dynamic t-SNARE complex in exocytosis is uncertain; however, it does take us one step closer to understand the complex sequence of events leading to vesicle fusion, emphasizing the role of both membrane proteins and lipids.
突触融合相关蛋白（SNARE）家族成员，包括突触融合蛋白（syntaxin）、突触相关蛋白 25（SNAP-25）和囊泡相关膜蛋白（synaptobrevin），长期以来一直被认为是调控性胞吐作用中囊泡融合的驱动力。特别值得关注的是，SNAP-25 与 syntaxin 之间的初始相互作用形成 t-SNARE 异二聚体，这是随后 synaptobrevin 结合的接受体。体外研究揭示了 t-SNARE 异二聚体至少存在两种不同的动态构象，这取决于 SNAP-25 的 C 端 SNARE 基序与 syntaxin 的结合程度。在质膜上，这些蛋白以直径为 50-60nm 的致密簇形式存在。最近，在活细胞中对这些簇内的 t-SNARE 相互作用进行了分子水平的研究，估计每个簇含有 35-70 个 t-SNARE 分子。这项工作报告了在质膜上存在部分和完全拉链式 t-SNARE 复合物，这与早期的体外发现一致。它还揭示了一种空间分隔成不同的簇，这些簇主要包含一种构象，显然是由周围的脂质环境模式化的。这种动态 t-SNARE 复合物在胞吐作用中的存在原因尚不确定；然而，它确实让我们更接近理解导致囊泡融合的复杂事件序列，强调了膜蛋白和脂质的作用。
