Abstract
Synapses are fundamental information processing units that rely on voltage-gated Ca2+ (Cav) channels to trigger Ca2+-dependent neurotransmitter release. Cav 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 Cav1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Cav1.4, we report that the Cav1.4 protein, but not its Ca2+ conductance, is required for the molecular assembly of rod synapses; however, Cav1.4 Ca2+ signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Cav 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.
Highlights
It is well established that the primary function of voltage-gated Cav Ca2+ channels within axon terminals is to serve as a conduit for Ca2+ ions that trigger the fusion of neurotransmitter-laden vesicles with the presynaptic membrane
During the first postnatal week in mice, ribbons develop from spherical precursors and are concentrated in the outer plexiform layer (OPL) where mature rod and cone synapses are localized (Blanks et al, 1974; Regus-Leidig et al, 2009)
In Cav1.4 KO mice, the development of these synapses appears stunted in that spheres, rather than ribbons, are present at all developmental ages and often found in the outer nuclear layer (ONL) that normally contains only photoreceptor somas
Summary
It is well established that the primary function of voltage-gated Cav Ca2+ channels within axon terminals is to serve as a conduit for Ca2+ ions that trigger the fusion of neurotransmitter-laden vesicles with the presynaptic membrane (reviewed in Dolphin and Lee, 2020). An additional contributing factor is that photoreceptor synapses do not form in Cav1.4 KO mice (Liu et al, 2013; Zabouri and Haverkamp, 2013; Regus-Leidig et al, 2014). Does this developmental failure reflect a requirement for Cav1.4-mediated Ca2+ signals or an alternative, non-conducting role for the Cav1.4 protein in organizing the photoreceptor synapse? Does this developmental failure reflect a requirement for Cav1.4-mediated Ca2+ signals or an alternative, non-conducting role for the Cav1.4 protein in organizing the photoreceptor synapse? Here, we generated a mouse strain that expresses a nonconducting mutant form of Cav1.4 to answer this question
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