A dual role for Ca(v)1.4 Ca(2+) channels in the molecular and structural organization of the rod photoreceptor synapse

Synapses are fundamental information processing units that rely on voltage-gated Ca(2+) (Ca(v)) channels to trigger Ca(2+)-dependent neurotransmitter release. Ca(v) channels also play Ca(2+)-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Ca(v)1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Ca(v)1.4, we report that the Ca(v)1.4 protein, but not its Ca(2+) conductance, is required for the molecular assembly of rod synapses; however, Ca(v)1.4 Ca(2+) signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Ca(v) channels serve both as organizers of synaptic building blocks and as sources of Ca(2+) ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system.