Dueling Ca2+ sensors in neurotransmitter release

Abstract

Ca(2+)-triggered neurotransmitter release is characterized by two kinetically distinct components: a fast synchronous phase and a slow asynchronous phase. Yao et al. (2011) now report that double C2 domain (Doc2) proteins function as high-affinity Ca(2+) sensors to specifically regulate the asynchronous component of neurotransmitter release.

Figure 1

Ca²⁺ Sensors Synaptotagmin I and Doc2 Trigger Evoked Neurotransmitter Release (A) Action potentials open voltage-gated calcium channels, resulting in a brief and high-concentration influx of Ca²⁺. The C2A and C2B domains of synaptotagmin I bind to Ca²⁺ and interact with phospholipid membranes and SNAREs to trigger synchronous neurotransmitter release. (B) Following the termination of action potentials, intracellular Ca²⁺ concentration decays to a much lower level. Doc2 binds to this residual Ca²⁺ and triggers asynchronous release, possibly through a mechanism similar to that of synaptotagmin I.