Translating neuronal activity at the synapse: presynaptic calcium sensors in short-term plasticity

The complex manner in which patterns of presynaptic neural activity ate translated into short-term plasticity (SIP) suggests the existence of multiple presynaptic calcium (Ca2+ sensors, which regulate the amplitude and time-course of SIP and are the focus of this review. We describe two canonical Ca2+-binding protein domains (C2 domains and FE-hands) and define criteria that need to be met for a protein to qualify as a Ca2+ sensor mediating SIR With these criteria in mind, we discuss various forms of SIR and identify established and putative Ca2+ sensors. We find that despite the multitude of proposed sensors, only three are well established in SIP: Munc13, protein kinase C (PKC) and synaptotagmin-7 For putative sensors, we pinpoint open questions and potential pitfalls. Finally, we discuss how the molecular properties and modes of action of Ca2+ sensors can explain their differential involvement in SIP and shape net synaptic output.