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The Auxiliary Calcium Channel Subunit ?2?4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors.

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 Ca2+ channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, ?2?4, which complexes with CaV1.4 and the rod synaptogenic mediator, ELFN1, for trans-synaptic alignment with mGluR6. Eliminating ?2?4 in mice abolishes rod synaptogenesis and synaptic transmission to rod ON-bipolar cells, and disrupts postsynaptic mGluR6 clustering. We further find that in rods, ?2?4 is crucial for organizing synaptic ribbons and setting CaV1.4 voltage sensitivity. In cones, ?2?4 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 ?2?4 dysfunction.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5364038 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Wang Yuchen Y Fehlhaber Katherine E KE Sarria Ignacio I Cao Yan Y Ingram Norianne T NT Guerrero-Given Debbie D Throesch Ben B Baldwin Kristin K Kamasawa Naomi N Ohtsuka Toshihisa T Sampath Alapakkam P AP Martemyanov Kirill A KA

Neuron 20170302 6

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<sup>2+</sup> channel directing glutamate release (Ca<sub>V</sub>1.4) with postsynaptic mGluR6 receptors. We sho ...[more]

PMID: 28262416

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Dataset Information

The Auxiliary Calcium Channel Subunit ?2?4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors.

Publications

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

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