| First Author | Wang Y | Year | 2017 |
| Journal | Neuron | Volume | 93 |
| Issue | 6 | Pages | 1359-1374.e6 |
| PubMed ID | 28262416 | Mgi Jnum | J:256152 |
| Mgi Id | MGI:6114199 | Doi | 10.1016/j.neuron.2017.02.021 |
| Citation | Wang Y, et al. (2017) The Auxiliary Calcium Channel Subunit alpha2delta4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors. Neuron 93(6):1359-1374.e6 |
| abstractText | 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 (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, alpha2delta4, which complexes with CaV1.4 and the rod synaptogenic mediator, ELFN1, for trans-synaptic alignment with mGluR6. Eliminating alpha2delta4 in mice abolishes rod synaptogenesis and synaptic transmission to rod ON-bipolar cells, and disrupts postsynaptic mGluR6 clustering. We further find that in rods, alpha2delta4 is crucial for organizing synaptic ribbons and setting CaV1.4 voltage sensitivity. In cones, alpha2delta4 is essential for CaV1.4 function, but is not required for ribbon organization, synaptogenesis, or synaptic transmission. These findings offer insights into retinal pathologies associated with alpha2delta4 dysfunction. |
