Synaptotagmin I, a Ca2+ sensor for neurotransmitter release

The discovery that Ca2+ triggers rapid neurotransmitter release has prompted the search for the Ca2+ sensor. There is now general agreement that the vesicle-associated Ca2+-binding protein, synaptotagmin I, is required for the tight temporal coupling between Ca2+ influx and synaptic vesicle fusion. However, the precise mechanism of Ca2+-sensing by synaptotagmin I is still under debate despite intensive investigation using genetic, biochemical and electrophysiological tools. Here, we discuss many of the genetic manipulations from the past few years that have shed light on the Ca2+-sensing function of synaptotagmin I. We also present our view as to how the Ca2+ signal is translated rapidly into membrane fusion at fast chemical synapses.