Plasmenylethanolamine facilitates rapid membrane fusion
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Glaser PE and Gross RW. (1994) Plasmenylethanolamine facilitates rapid membrane fusion: A stopped-flow kinetic investigation correlating the propensity of a major plasma membrane constituent to adopt an HII phase with its ability to promote membrane fusion. Biochemistry, 33: 5805-5812
Membrane fusion is a process where separate lipid membranes join and become one continuous membrane, which is required for synaptic transmission, hormone release, and membrane trafficking to occur. It is well established that fusion proteins need to be present on the membranes in order for membranes to recognize and anchor together. It is also known that the phospholipid composition of the membrane plays an important role. Glaser and Gross’ work almost 30 years ago was seminal to our understanding of the role of the vinyl-ether bond, found in a unique class of lipids called plasmalogens, on rates of membrane fusion. To accomplish these studies, plasmalogen ethanolamines (PlsEtns) were synthesized and stopped-flow kinetics and membrane fusion assays were employed.
To evaluate whether vesicles containing PlsEtns or phosphatidylethanolamines (PtdEtns) had a higher proclivity for membrane fusion, stopped-flow kinetics was used to quantify the rate of fusion. The vesicles were synthesized to contain either 16:0/18:1 PlsEtn, 16:0/18:1 PtdEtn, 18:0/20:4 PlsEtn, or 18:0/20:4 PtdEtn. The vesicles containing 16:0/18:1 PlsEtn had a three-fold greater rate of membrane fusion compared to 16:0/18:1 PtdEtn. Further, 18:0/20:4 PlsEtn had a two-fold higher rate of fusion compared to 16:0/18:1 PlsEtn. While the vinyl bond was not a requirement for membrane fusion to occur, since membrane fusion still occurred in vesicles containing PtdEtn, it was found to favor fusion. Interestingly, the presence of a vinyl bond was found to be as important as the presence of an arachidonoyl fatty acid at sn-2 since 18:0/20:4 PtdEtn almost the same rate of fusion as 16:0/18:1 PlsEtn, however the vesicles containing 18:0/20:4 PlsEtn showed the greatest rate of fusion.
To confirm whether PlsEtn fosters fusion more than PtdEtn, a fusion assay was used with mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and many ethanolamine glycerophospholipids. It was found that PlsEtn causes an increase in membrane fusion rates as the vesicles with 16:0/18:1 PlsEtn showed six times more fusion than those with 16:0/18:1 PtdEtn.
These findings from Glaser and Gross describing how a higher presence of lipids with a vinyl bond resulted in a faster rate of membrane fusion and increased fusogenic ability have been fundamental to the field of plasmalogen research. This work provided support for the theory that plasmalogens play a central role in neurotransmission, a process dependent on membrane fusion. Subsequent studies have been able to build off this knowledge to further implicate the role of plasmalogens in processes involving membrane fusion. Today this has lead to a hypothesis that the plasmalogen defiency observed in diseases such as Alzheimer’s and Parkinson’s disease could be driving disease pathology through impaired neuronal function.