The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors.

Autor: Wang Y; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA., Fehlhaber KE; Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA 90095, USA., Sarria I; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA., Cao Y; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA., Ingram NT; Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA 90095, USA., Guerrero-Given D; Electron Microscopy Core Facility, Max Planck Florida Institute, 1 Max Planck Way, Jupiter, FL 33458, USA., Throesch B; Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92121, USA., Baldwin K; Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92121, USA., Kamasawa N; Electron Microscopy Core Facility, Max Planck Florida Institute, 1 Max Planck Way, Jupiter, FL 33458, USA., Ohtsuka T; Department of Biochemistry, University of Yamanashi, Yamanashi 409-3898, Japan., Sampath AP; Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA 90095, USA., Martemyanov KA; Department of Neuroscience, The Scripps Research Institute, Jupiter, FL 33458, USA. Electronic address: kirill@scripps.edu.
Jazyk: angličtina
Zdroj: Neuron [Neuron] 2017 Mar 22; Vol. 93 (6), pp. 1359-1374.e6. Date of Electronic Publication: 2017 Mar 02.
DOI: 10.1016/j.neuron.2017.02.021
Abstrakt: 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 (Ca V 1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with Ca V 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 Ca V 1.4 voltage sensitivity. In cones, α2δ4 is essential for Ca V 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.)
Databáze: MEDLINE
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