Wang Hongbing, Zhang Chengliang, Xiao Hua
Department of Physiology, Michigan State University East Lansing, Michigan 48824, USA.
Neuroscience Program, Michigan State University East Lansing, Michigan 48824, USA.
Int J Physiol Pathophysiol Pharmacol. 2019 Dec 15;11(6):250-257. eCollection 2019.
Membrane fusion is a universal event in all living organism. It is at the heart of intracellular organelle biogenesis and membrane traffic processes such as endocytosis and exocytosis, and is also used by enveloped viruses to enter hosting cells. Regarding the cellular mechanisms underlying membrane fusion, pioneering studies by Randy Schekman, James Rothman, Thomas C. Südhof and their colleagues have demonstrated the function of specific proteins and protein-protein interactions as essential fusogenic factor to initiate membrane fusion. Since then, function of lipids and protein-lipid interaction has also been identified as important players in membrane fusion. Based on that NSF (NEM-sensitive factor where NEM stands for -ethyl-maleimide) and acyl-CoA are required for the membrane fusion of transporting vesicles with Golgi cisternae, it is further suggested that the transfer of the acyl chain to a molecule(s) is essential for membrane fusion. Among the previously identified fusogens, phosphatidic acid (PA) is found as an acyl chain recipient. Functionally, acylation of PA is required for tethering the membranes of Rab5a vesicles and early endosomes together during membrane fusion. As certain threshold of proximity between the donor and acceptor membrane is required to initiate membrane fusion, fusogenic factors beyond protein-protein and protein-lipid interaction need to be identified.
膜融合是所有生物中的普遍现象。它是细胞内细胞器生物发生以及诸如内吞作用和胞吐作用等膜运输过程的核心，包膜病毒也利用它进入宿主细胞。关于膜融合的细胞机制，兰迪·谢克曼、詹姆斯·罗斯曼、托马斯·C·聚德霍夫及其同事的开创性研究表明，特定蛋白质和蛋白质 - 蛋白质相互作用作为启动膜融合的必需融合因子发挥作用。从那时起，脂质和蛋白质 - 脂质相互作用的功能也被确定为膜融合中的重要参与者。基于运输小泡与高尔基体潴泡的膜融合需要 NSF（NEM 敏感因子，其中 NEM 代表 N - 乙基 - 马来酰亚胺）和酰基辅酶 A，进一步表明酰基链向一个或多个分子的转移对于膜融合至关重要。在先前确定的融合蛋白中，磷脂酸（PA）被发现是酰基链受体。在功能上，PA 的酰化是膜融合过程中将 Rab5a 小泡和早期内体的膜拴在一起所必需的。由于启动膜融合需要供体膜和受体膜之间达到一定的接近阈值，因此需要鉴定除蛋白质 - 蛋白质和蛋白质 - 脂质相互作用之外的融合因子。
