Lang Thorsten, Halemani Nagaraj D, Rammner Burkhard
LIMES-Institute, Laboratory for Membrane Biochemistry, University of Bonn, 53115 Bonn, Germany.
Prog Lipid Res. 2008 Nov;47(6):461-9. doi: 10.1016/j.plipres.2008.08.002. Epub 2008 Sep 19.
For membrane fusion to occur, opposed lipid bilayers initially establish a fusion pore, often followed by complete mixing of the fusing membranes. Contemporary views suggest that during fusion lipid bilayers are continuous passive platforms that are disrupted and remodeled by catalytic proteins. Some models propose that even the architecture and composition of the fusion pore might be dominated by proteins rather than lipids. Hence, lipids have no regulatory contribution to this process; they simply adapt their shape passively for filling space between otherwise autonomous protein machineries. However, an increasing number of experimental findings indicate that membrane fusion critically depends on a variety of lipids and lipid derivatives. Therefore, a purely proteocentric view describes fusion mechanisms insufficiently. Instead, lipids have functions probably at different levels, as (i) a general influence on the propensity of lipid bilayers to fuse, (ii) a role in recruiting exocytotic proteins to the plasma membrane, (iii) a role in organizing membrane domains for fusion and (iv) direct regulatory effects on fusion protein complexes. In this review we have made an attempt to bring together the large body of evidence supporting a major role for lipids in membrane fusion either directly or indirectly.
为了发生膜融合，相对的脂质双层最初会形成一个融合孔，随后通常是融合膜的完全混合。当代观点认为，在融合过程中，脂质双层是连续的被动平台，会被催化蛋白破坏并重塑。一些模型提出，甚至融合孔的结构和组成可能由蛋白质而非脂质主导。因此，脂质对这一过程没有调节作用；它们只是被动地改变形状以填充原本自主的蛋白质机器之间的空间。然而，越来越多的实验结果表明，膜融合严重依赖于多种脂质和脂质衍生物。因此，纯粹以蛋白质为中心的观点不足以描述融合机制。相反，脂质可能在不同层面发挥作用，如（i）对脂质双层融合倾向的一般影响，（ii）在将胞吐蛋白招募到质膜中的作用，（iii）在组织用于融合的膜结构域中的作用，以及（iv）对融合蛋白复合物的直接调节作用。在这篇综述中，我们试图汇集大量直接或间接支持脂质在膜融合中起主要作用的证据。
