Mechanism of membrane fusion: protein-protein interaction and beyond

Abstract

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 N-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.

Keywords: ACSL4; Acyl-CoA; Endo B1; NSF; Rab5a; SNARE; Tip30; endosome; lysosome; membrane fusion; phosphatidic acid.