Short-chain alcohols promote an early stage of membrane hemifusion
Short-chain alcohols promote an early stage of membrane hemifusion
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DOI：
10.1016/s0006-3495(99)77044-x
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发表时间：
1999-10-01
影响因子：
3.4
通讯作者：
Chernomordik, LV
中科院分区：
文献类型：
--
作者：
Chanturiya, A;Leikina, E;Chernomordik, LV
半融合是两个膜的脂质单层在融合孔打开之前接触的连接，推测是通过形成茎中间体进行的，茎中间体是膜之间的局部且强烈弯曲的连接。当单层的弯曲倾向不支持茎时（例如，当添加溶血磷脂酰胆碱时），半融合被抑制。相比之下，据报道，短链醇以与溶血磷脂酰胆碱类似的方式影响单层弯曲，在这里发现短链醇可以促进荧光标记的脂质体和平面脂质双层之间的半融合。通过荧光显微镜检测到单半融合事件。将甲醇或乙醇 (1.2-1.6 w/w %) 添加到平面双层室的同一隔室中作为脂质体，导致半融合事件数量增加 5-50 倍。溶血磷脂酰胆碱可抑制酒精引起的半融合。还观察到短链酒精促进流感病毒血凝素（HA）介导的细胞间融合的膜半融合。酒精促进了 HA 的低 pH 依赖性激活后的融合阶段。我们提出，短链醇与膜表面的结合通过促进每个接触单层的连续性的瞬时破坏来促进半融合，这是它们随后在茎中间体中合并所必需的。
Hemifusion, the linkage of contacting lipid monolayers of two membranes before the opening of a fusion pore, is hypothesized to proceed through the formation of a stalk intermediate, a local and strongly bent connection between membranes, When the monolayers' propensity to bend does not support the stalk (e.g., as it is when lysophosphatidylcholine is added), hemifusion is inhibited. In contrast, short-chain alcohols, reported to affect monolayer bending in a manner similar to that of lysophosphatidylcholine, were here found to promote hemifusion between fluorescently labeled liposomes and planar lipid bilayers, Single hemifusion events were detected by fluorescence microscopy. Methanol or ethanol (1.2-1.6 w/w %) added to the same compartment of the planar bilayer chamber as liposomes caused a 5-50 times increase in the number of hemifusion events. Alcohol-induced hemifusion was inhibited by lysophosphatidylcholine. Promotion of membrane hemifusion by short-chain alcohol was also observed for cell-cell fusion mediated by influenza virus hemagglutinin (HA). Alcohol promoted a fusion stage subsequent to the low pH-dependent activation of HA. We propose that binding of short-chain alcohol to the surface of membranes promotes hemifusion by facilitating the transient breakage of the continuity of each of the contacting monolayers, which is required for their subsequent merger in the stalk intermediate.