Membrane permeability changes at early stages of influenza hemagglutinin-mediated fusion
Membrane permeability changes at early stages of influenza hemagglutinin-mediated fusion
复制标题
DOI：
10.1016/s0006-3495(03)74602-5
复制
发表时间：
2003-09-01
影响因子：
3.4
通讯作者：
Zimmerberg, J
中科院分区：
文献类型：
--
作者：
Frolov, VA;Dunina-Barkovskaya, AY;Zimmerberg, J
虽然生物膜融合被经典地定义为膜和内容物的无泄漏合并，但泄漏是实验和理论研究中的发现。允许膜渗透的融合阶段（如果有的话）是未知的。在这项研究中，我们监测膜离子渗透性在融合蛋白流感血凝素（HA）介导的融合的早期阶段。HAb 2细胞，在其质膜上表达HA，与人红细胞、培养的肝细胞PLC/PRF/5或平面磷脂双层膜融合。在取决于靶膜的概率下，通常检测到融合膜的电导（泄漏）增加高达几个nS。这种渗漏是在融合的初始阶段记录的，当时形成了融合孔。这种渗漏通常伴随着早期熔合孔发育的“闪烁”阶段。随着孔变宽，渗漏减少;同时，融合膜之间的脂质交换加速。我们得出结论，在融合孔形成，HA局部和暂时增加融合膜的渗透性。随后在融合复合物中的重排导致渗漏膜的重新密封和孔的扩大。
While biological membrane fusion is classically defined as the leak-free merger of membranes and contents, leakage is a finding in both experimental and theoretical studies. The fusion stages, if any, that allow membrane permeation are uncharted. In this study we monitored membrane ionic permeability at early stages of fusion mediated by the fusogenic protein influenza hemagglutinin (HA). HAb2 cells, expressing HA on their plasma membrane, fused with human red blood cells, cultured liver cells PLC/PRF/5, or planar phospholipid bilayer membranes. With a probability that depended upon the target membrane, an increase of the electrical conductance of the fusing membranes (leakage) by up to several nS was generally detected. This leakage was recorded at the initial stages of fusion, when fusion pores formed. This leakage usually accompanied the "flickering'' stage of the early fusion pore development. As the pore widened, the leakage reduced; concomitantly, the lipid exchange between the fusing membranes accelerated. We conclude that during fusion pore formation, HA locally and temporarily increases the permeability of fusing membranes. Subsequent rearrangement in the fusion complex leads to the resealing of the leaky membranes and enlargement of the pore.