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Syt-12 (green) on synaptic vesicles increases spontaneous release of neurotransmitters.

On page 113, Maximov et al. show that a calcium-independent synaptotagmin (syt) enhances the spontaneous release of neurotransmitters. By linking to another syt that does respond to calcium, the calcium-independent syt might also alter evoked neurotransmitter release.

There are many synaptotagmins, but only syt-1 and syt-2 have a well-defined function, which is to trigger the release of neurotransmitters in response to calcium. Syt-12 does not bind to calcium, yet the authors found it is still localized to synaptic vesicles.

To understand its function, the authors expressed syt-12 in cultured neurons, which did not make their own endogenous version. The presence of syt-12 increased the spontaneous release of neurotransmitter in these neurons.

The function of spontaneous release is controversial: some neuroscientists believe these release events are physiologically important for neuronal structure and function, whereas others...

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