A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse

Synapses are fundamental information processing units that rely on voltage-gated Ca²⁺ (Ca_v) channels to trigger Ca²⁺-dependent neurotransmitter release. Ca_v channels also play Ca²⁺-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_v1.4 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_v1.4, we report that the Ca_v1.4 protein, but not its Ca²⁺ conductance, is required for the molecular assembly of rod synapses; however, Ca_v1.4 Ca²⁺ 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 Ca²⁺ ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system.