Unraveling the mechanisms of synaptotagmin and SNARE function in neurotransmitter release

SNARE proteins and synaptotagmin are key components of the complex machinery that controls Ca2+-triggered neurotransmitter release but their mechanisms of action are under debate. Recent research has shed light on which biochemical and/or biophysical properties underlie SNARE and synaptotagmin function. SNARE proteins most likely have a role in membrane fusion owing to their ability to bring the synaptic vesicle and plasma membranes together and to perturb lipid bilayers through their transmembrane regions. Synaptotagmin acts as a Ca2+ sensor and might cooperate with the SNAREs in accelerating fusion by binding simultaneously to the two membranes. However, recent research has strongly challenged the validity of models proposing that the SNAREs (with or without synaptotagmin) constitute ‘minimal membrane fusion machineries’ and has emphasized the essential nature of other proteins for exocytosis. Understanding the functions of these proteins will be crucial to reach a faithful description of the mechanisms of membrane fusion and neurotransmitter release.