Nanodomain coupling between Ca2+ channels and sensors of exocytosis at fast mammalian synapses

The efficacy of synaptic transmission depends on the coupling between presynaptic calcium channels and the molecules that trigger exocytosis in response to calcium influx. Jonas and colleagues describe evidence for tight coupling at certain fast mammalian synapses, its contribution to signalling properties and the underlying protein–protein interactions. The physical distance between presynaptic Ca2+ channels and the Ca2+ sensors that trigger exocytosis of neurotransmitter-containing vesicles is a key determinant of the signalling properties of synapses in the nervous system. Recent functional analysis indicates that in some fast central synapses, transmitter release is triggered by a small number of Ca2+ channels that are coupled to Ca2+ sensors at the nanometre scale. Molecular analysis suggests that this tight coupling is generated by protein–protein interactions involving Ca2+ channels, Ca2+ sensors and various other synaptic proteins. Nanodomain coupling has several functional advantages, as it increases the efficacy, speed and energy efficiency of synaptic transmission.