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Fusion has found its calcium sensor

Nature Cell Biology volume 6, pages 476–478 (2004)Cite this article

Synaptic vesicle exocytosis, a finely tuned process that results in rapid neurotransmitter release, is still not fully understood. Studies in a simple reconstituted lipid bilayer system have now definitively demonstrated that synaptotagmin has a key role in calcium-mediated exocytosis and have also revealed additional aspects of exocytic fusion.

The series of events resulting in neurotransmitter release at synaptic terminals have been the subject of intense investigation for decades. The key issue has been defining the machinery necessary for synaptic vesicle fusion. Among secretory processes, neurotransmitter release is unique, particularly in its spatial and temporal resolution. In resting terminals, a part of the vesicle population is already primed to fuse. These vesicles are strategically docked at specific sites of the presynaptic plasma membrane that are in immediate proximity to voltage-gated calcium channels. Activation of these channels (a consequence of plasma membrane depolarization induced by the action potential) results in the vesicles being flooded with calcium at concentrations three orders of magnitude higher than in resting cells, and this drives their rapid exocytic fusion within less than 1 ms. Work from Tucker et al., published in Science, now provides insights into the calcium-dependence of this process1.

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Figure 1: The in vitro fusion assay.
Figure 2: Differential effects of C2AB using subcellular fractions and artificial bilayers.

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Affiliations

  1. Department of Neuroscience, Vita-Salute San Raffaele University, Center of Excellence in Cellular Pathophysiology

    Jacopo Meldolesi & Evelina Chieregatti

  2. Scientific Institute San Raffaele, DIBIT, Via Olgettina 58, Milan, 20132, Italy

    Jacopo Meldolesi & Evelina Chieregatti

Authors
  1. Jacopo Meldolesi
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  2. Evelina Chieregatti
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Meldolesi, J., Chieregatti, E. Fusion has found its calcium sensor. Nat Cell Biol 6, 476–478 (2004). https://doi.org/10.1038/ncb0604-476

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  • DOI: https://doi.org/10.1038/ncb0604-476

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