Editors' ChoiceNeuroscience

“Spontaneous” Release Trigger

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Science Signaling  30 Mar 2010:
Vol. 3, Issue 115, pp. ec101
DOI: 10.1126/scisignal.3115ec101

Synaptic vesicle release occurs in different phases that can be tightly coupled to action potentials (synchronous), immediately following action potentials (asynchronous), or stochastic events not triggered by action potentials (spontaneous). The vesicle protein synaptotagmin is thought to act as the Ca2+ sensor in the synchronous phase, but for the other two phases, Ca2+ sensors have not been identified. Groffen et al. now show that cytoplasmic proteins known as Doc2 (double C2 domain) proteins are required for spontaneous release. Doc2 proteins promote membrane fusion in response to exceptionally low increases in Ca2+ and are several orders of magnitude more sensitive to Ca2+ than synaptotagmin. Doc2 and synaptotagmin compete for SNARE-complex binding during membrane fusion. A mutation that abolishes the Ca2+ dependence of Doc2b also abolishes the Ca2+ dependence of spontaneous release. Thus, Doc2 is a high-affinity Ca2+ sensor for spontaneous release that competes with synaptotagmin for SNARE complex binding.

A. J. Groffen, S. Martens, R. Díez Arazola, L. N. Cornelisse, N. Lozovaya, A. P. H. de Jong, N. A. Goriounova, R. L. P. Habets, Y. Takai, J. G. Borst, N. Brose, H. T. McMahon, M. Verhage, Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release. Science 327, 1614–1618 (2010). [Abstract] [Full Text]

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