Abstract
Membrane fusion is a key process in all living organisms that contributes to a variety of biological processes including viral infection, cell fertilization, as well as intracellular transport, and neurotransmitter release. In particular, the various membrane-enclosed compartments in eukaryotic cells need to exchange their contents and communicate across membranes. Efficient and controllable fusion of biological membranes is known to be driven by cooperative action of SNARE proteins, which constitute the central components of the eukaryotic fusion machinery responsible for fusion of synaptic vesicles with the plasma membrane. During exocytosis, vesicle-associated v-SNARE (synaptobrevin) and target cell-associated t-SNAREs (syntaxin and SNAP-25) assemble into a core trans-SNARE complex. This complex plays a versatile role at various stages of exocytosis ranging from the priming to fusion pore formation and expansion, finally resulting in the release or exchange of the vesicle content. This review summarizes current knowledge on the intricate molecular mechanisms underlying exocytosis triggered and catalyzed by SNARE proteins. Particular attention is given to the function of the peptidic SNARE membrane anchors and the role of SNARE-lipid interactions in fusion. Moreover, the regulatory mechanisms by synaptic auxiliary proteins in SNARE-driven membrane fusion are briefly outlined.
Highlights
Biological membranes separate the cell interior from its environment and allow for the compartmentalization within the cell
The formation of the fusion pore was suggested to be initiated by the movement of the sybII transmembrane domains (TMDs) uncharged C-terminus into the membrane interior, induced by the pulling force resulting from SNARE complex zippering, as revealed by coarse-grained simulations (Lindau et al, 2012)
Apart from the SNARE complex that is characterized as the energy machinery in intracellular exocytosis, a set of regulatory proteins such as Munc18-1 (SM), synaptotagmin, and complexin in eukaryotic cells have been demonstrated to be essential for exocytosis as well
Summary
Biological membranes separate the cell interior from its environment and allow for the compartmentalization within the cell. They are involved in a variety of cellular events, e.g., cell signaling, exocytosis, and ion conductance. Membrane fusion is the process by which two initially separated lipid bilayers merge to form a single unity. It is a universal biological process in life, that is involved in many cellular events, e.g., in viral infection, fertilization, and intracellular trafficking. The energy required to overcome the energy barrier for the fusion of biological membranes is provided by specialized fusion proteins, e.g., in exocytosis the. The known regulatory mechanism by auxiliary proteins are briefly reviewed
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