Molecular machines governing exocytosis of synaptic vesicles

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Abstract
A brief survey of the molecular mechanisms that give the vesicle cycle in intact synapses its efficiency. Fast neurotransmission at synapses relies crucially on a series of membrane trafficking and signalling proteins, such as SNAREs, synaptotagmins and complexins. However, recent results have been hard to integrate into a consistent picture of how these enable calcium-dependent fusion of synaptic vesicles. In this Review, Reinhard Jahn and Dirk Fasshauer unify the latest biochemical and biophysical data with older knowledge to propose a fresh view of the field of synaptic transmission. Calcium-dependent exocytosis of synaptic vesicles mediates the release of neurotransmitters. Important proteins in this process have been identified such as the SNAREs, synaptotagmins, complexins, Munc18 and Munc13. Structural and functional studies have yielded a wealth of information about the physiological role of these proteins. However, it has been surprisingly difficult to arrive at a unified picture of the molecular sequence of events from vesicle docking to calcium-triggered membrane fusion. Using mainly a biochemical and biophysical perspective, we briefly survey the molecular mechanisms in an attempt to functionally integrate the key proteins into the emerging picture of the neuronal fusion machine.

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