1. The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors.
- Author
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Wang Y, Fehlhaber KE, Sarria I, Cao Y, Ingram NT, Guerrero-Given D, Throesch B, Baldwin K, Kamasawa N, Ohtsuka T, Sampath AP, and Martemyanov KA
- Subjects
- Animals, Calcium Channels, L-Type genetics, Calcium Channels, L-Type metabolism, Cells, Cultured, Female, Humans, Male, Mice, Mice, Knockout, Mice, Mutant Strains, Nerve Tissue Proteins metabolism, Receptors, Metabotropic Glutamate physiology, Retinal Bipolar Cells physiology, Retinal Cone Photoreceptor Cells physiology, Synapses metabolism, Axons physiology, Calcium Channels physiology, Calcium Channels, L-Type physiology, Retinal Rod Photoreceptor Cells physiology, Synaptic Transmission physiology
- Abstract
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca
2+ channel directing glutamate release (CaV 1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with CaV 1.4 and the rod synaptogenic mediator, ELFN1, for trans-synaptic alignment with mGluR6. Eliminating α2δ4 in mice abolishes rod synaptogenesis and synaptic transmission to rod ON-bipolar cells, and disrupts postsynaptic mGluR6 clustering. We further find that in rods, α2δ4 is crucial for organizing synaptic ribbons and setting CaV 1.4 voltage sensitivity. In cones, α2δ4 is essential for CaV 1.4 function, but is not required for ribbon organization, synaptogenesis, or synaptic transmission. These findings offer insights into retinal pathologies associated with α2δ4 dysfunction., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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