Please release me.

In this issue of Neuron, Südhof and colleagues determine which of the eight Ca(2+)-binding synaptotagmin isoforms expressed in brain can support synchronous neurotransmitter release at mammalian CNS synapses. Unexpectedly, only three-synaptotagmin-1, -2, and -9-can serve as Ca(2+) sensors for fast transmission. Further characterization reveals the unique ability of each isoform to shape neurotransmission.