title: Characterization of the cystine/glutamate transporter in the outer plexiform layer of the vertebrate retina.
abstract: The cystine/glutamate transporter (Xc-) is widely expressed in the central nervous system and is thought to play a role in glutamatergic neurotransmission by releasing low levels of glutamate. Although previous studies have localized the transporter throughout the retina, we now present results from localization and functional studies within the first synaptic layer, i.e. the outer plexiform layer. Using light and electron microscopy, we have localized the Xc- transporter to the ribbon complex of both rod and cone photoreceptors in the rat, cow, lamprey, chicken and monkey retina, suggesting that the pre-synaptic expression of the Xc- transporter on the photoreceptor ribbon complex is phylogenetically preserved. The Xc- transporter does not appear to be located within the ribbon synapse of the inner plexiform layer. Developmentally, the evolution of distinct ribbon-shaped Xc- labelling in the outer plexiform layer parallels the known morphological and electrophysiological maturation of photoreceptors. Using the cation channel probe agmatine, we tracked cation fluxes within bipolar cells and therefore indirectly determined the modulation of glutamate release from photoreceptors. Such cystine-driven alteration in agmatine entry into bipolar cells can be modified by a specific metabotropic glutamate receptor 6 antagonist [(RS)-alpha-cyclopropyl-4-phosphonophenylglycine] and an Xc- transport inhibitor [(S)-4-carboxyphenylglycine]. The phylogenetic preservation of the transporter, its ultrastructural localization to the ribbon synapse and functional modulation of post-receptoral neurons collectively support a role for the Xc- transporter in glutamate neurotransmission in the outer retina of vertebrates. We have therefore proposed a model of glutamate release in the photoreceptor synapse that incorporates the Xc- transporter, which complements the established vesicular-mediated glutamate release.
authors.affiliation: Department of Optometry and Vision Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Hu
authors.forename: Julie
authors.initials: J
authors.lastname: Lim
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Donaldson
authors.forename: Michael
authors.initials: M
authors.lastname: Kalloniatis
mesh_terms: D000376:Agmatine / Q000494:pharmacology; D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D027682:Cation Transport Proteins / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002645:Chickens; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019143:Evolution, Molecular; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D000882:Haplorhini; D007798:Lampreys; D016253:Microscopy, Immunoelectron; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010802:Phylogeny; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000648:ultrastructure; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013045:Species Specificity; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D027182:Amino Acid Transport System y+; D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C492255:Slc7a11 protein, mouse; C113897:metabotropic glutamate receptor 6; D018698:Glutamic Acid; D000376:Agmatine