Abstract：
Lipids are key factors in regulating membrane fusion. Lipids are not only structural components to form membranes but also active catalysts for vesicle fusion and neurotransmitter release, which are driven by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. SNARE proteins seem to be partially assembled before fusion, but the mechanisms that arrest vesicle fusion before Ca2+ influx are still not clear. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP2) electrostatically triggers vesicle fusion as an electrostatic catalyst by lowering the hydration energy and that a myristoylated alanine-rich C-kinase substrate (MARCKS), a PIP2-binding protein, arrests vesicle fusion in a vesicle docking state where the SNARE complex is partially assembled. Vesicle-mimicking liposomes fail to reproduce vesicle fusion arrest by masking PIP2, indicating that native vesicles are essential for the reconstitution of physiological vesicle fusion. PIP2 attracts cations to repel water molecules from membranes, thus lowering the hydration energy barrier.
摘要：
脂质是调节膜融合的关键因素。脂质不仅是形成膜的结构成分，而且是囊泡融合和神经递质释放的活性催化剂，由可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白驱动。SNARE蛋白似乎在融合前部分组装，但是在Ca2流入之前阻止囊泡融合的机制仍然不清楚。这里,我们表明，磷脂酰肌醇4,5-二磷酸（PIP2）静电触发囊泡融合作为一种静电催化剂，通过降低水合能和肉豆蔻酰化的富含丙氨酸的C激酶底物（MARCKS），PIP2结合蛋白，在SNARE复合物部分组装的囊泡对接状态下阻止囊泡融合。囊泡模拟脂质体无法通过掩蔽PIP2来再现囊泡融合停滞，这表明天然囊泡对于生理囊泡融合的重建至关重要。PIP2吸引阳离子以排斥膜中的水分子，从而降低水合能量屏障。
