Molecular machines governing exocytosis of synaptic vesicles

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Abstract

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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Figure 1: Trafficking pathways in the nerve terminal.
Figure 2: Schematic depictions of domain structures and crystal structures of core proteins of the neuronal fusion machine.
Figure 3: Alternative models describing the steps between priming and fusion.
Figure 4: Transition states during membrane fusion.

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Acknowledgements

Work in the authors’ laboratories was supported by grants from the National Institutes of Health (3P01GM072694-05S1) to D.F. and R.J., of the Swiss National Fond to D.F. (31003A_133055) and of the Deutsche Forschungsgemeinschaft to D.F. (FA 297/3-1) and R.J. (SFB 803). The authors thank H. Grubmüller, E. Neher, J. Rissellada, G. van den Bogaart, M. Hernandez, J. Sørensen and J. Rizo for discussions and critical reading of the manuscript. We apologize to all colleagues whose work, although relevant, could not be mentioned and/or cited owing to space limitations.

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Correspondence to Reinhard Jahn.

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Jahn, R., Fasshauer, D. Molecular machines governing exocytosis of synaptic vesicles. Nature 490, 201–207 (2012) doi:10.1038/nature11320

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