Direct Visualization of Model Membrane Remodeling by α-Synuclein Fibrillization.
Direct Visualization of Model Membrane Remodeling by α-Synuclein Fibrillization.
复制标题
DOI：
10.1002/cphc.201700050
复制
发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Claessens MMAE
中科院分区：
文献类型：
--
作者：
Chaudhary H;Subramaniam V;Claessens MMAE
α -突触核蛋白（α s）与细胞膜的相互作用被认为在帕金森病的病因学中至关重要。除了低聚αS聚集体可能形成膜孔外，αS聚集成淀粉样原纤维也有报道破坏膜。然而，聚集影响膜完整性的机制尚不清楚。在这里，我们发现成熟的αS原纤维仅微弱地粘附在POPC/POPG巨型单层囊泡（GUVs）上，而αS在膜上的成纤维化导致了大规模的膜重塑。生长在囊泡表面的原纤维使膜变硬，使最初的球形膜变成多面体。此外，膜附着原纤维提取脂质。生长原纤维的脂质提取和膜重塑会消耗整个双层表面，导致囊泡含量的损失。这些观察结果表明，生长的原纤维可以破坏膜功能的几种机制。
The interaction of α‐synuclein (αS) with membranes is thought to be critical in the etiology of Parkinson's disease. Besides oligomeric αS aggregates that possibly form membrane pores, the aggregation of αS into amyloid fibrils has been reported to disrupt membranes. The mechanism by which aggregation affects the integrity of membranes is, however, unknown. Here, we show that whereas mature αS fibrils only weakly adhere to POPC/POPG giant unilamellar vesicles (GUVs), fibrillization of αS on the membrane results in large‐scale membrane remodeling. Fibrils that grow on the vesicle surface stiffen the membrane and make the initially spherical membrane become polyhedral. Additionally, membrane‐attached fibrils extract lipids. The lipid extraction and membrane remodeling of growing fibrils can consume the complete bilayer surface and results in loss of vesicle content. These observations suggest that there are several mechanisms by which growing fibrils can disrupt membrane function.