The t-SNARE Complex: A Close Up
The t-SNARE Complex: A Close Up
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DOI：
10.1007/s10571-010-9599-4
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发表时间：
2010-11-01
影响因子：
4
通讯作者：
Duncan, Rory R.
中科院分区：
文献类型：
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作者：
Dun, Alison R.;Rickman, Colin;Duncan, Rory R.
SNARE蛋白、突触融合蛋白、SNAP-25和小突触泡蛋白长期以来被认为在调节胞吐的过程中为囊泡融合提供驱动力。特别令人感兴趣的是SNAP-25和突触融合蛋白之间的初始相互作用，以形成t-SNARE异源二聚体，其是随后小突触泡蛋白接合的受体。体外研究已经揭示了由SNAP-25的C-末端SNARE基序与突触融合蛋白的缔合程度定义的t-SNARE异二聚体的至少两种不同的动态构象。在质膜上，这些蛋白质被组织成直径为50-60 nm的密集簇。最近，在活细胞中在分子水平上研究了这些簇内的t-SNARE相互作用，估计每个簇包含35-70个t-SNARE分子。这项工作报告了部分和完全拉链的t-SNARE复合物在质膜上的存在，与早期的体外研究结果一致。它还揭示了一个空间分离：到不同的集群包含主要是一个构象显然是由周围的脂质环境模式。胞吐中这种动态t-SNARE复合物的原因尚不确定;然而，它确实使我们更接近理解导致囊泡融合的事件的复杂序列，强调膜蛋白和脂质的作用。
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.