The process of membrane fusion is as old as life itself. The very birth of the unit of life, the cell, may well have taken place with the encapsulation of a primodial life-soup within a membranous sac, and the subsequent fission and fusion of membranes, ultimately giving birth to the various functionally specialized sub-cellular organelles as we know them today. Whatever may be the case, membrane fusion in cells is an essential and fundamental requirement, occurring in all life forms – from yeast to humans. The process is so fundamental, that without it, life essentially would cease to exist. Therefore, the quest to understand membrane fusion in cells has been on for more than a century. Only in the last 15 years, the molecular machinery and mechanism of the process has been brought to light with the pioneering discoveries of Bhanu P. Jena and James E. Rothman, in the field.
During the 1970’s, extensive studies by D. Papahadjopoulos and his research team , and later throughout the 1980’s, studies from various laboratories including that of S. Ohki [2, 3], clearly demonstrated the requirement of divalent cations, especially Ca2+ on fusion of opposing phospholipid membranes. Then, in the 1990’s [4, 5], James E. Rothman and his research team demonstrated that three soluble N-ethylmaleimide-sensitive factor (NSF)-attachment protein receptors (SNAREs), are universally involved in membrane fusion in mammalian cells [4, 5]. Target membrane proteins SNAP-25 and syntaxin, collectively termed t-SNAREs or target SNAREs, and secretory vesicle-associated membrane protein: VAMPor v-SNARE, are part of the conserved protein complex involved in fusion of opposing bilayers in cells. The discovery of SNARE proteins, and determination of their involvement in membrane fusion in cells, was truly a breakthrough, since for the first time, it provided an explanation for specificity and regulation of membrane fusion in cells. With the discovery of SNAREs, the requirement of Ca2+ on fusion of opposing phospholipid membranes was completely overlooked, so much so that SNAREs came to be recognized as the “minimal fusion machinery” . Nonetheless, the next major question i.e., the molecular mechanism of SNARE-induced fusion of opposing bilayers, remained unsolved.