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The Journal of Neuroscience, June 6, 2007, 27(23):6273-6281; doi:10.1523/JNEUROSCI.1024-07.2007
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Cellular/Molecular
The Transporters GlyT2 and VIAAT Cooperate to Determine the Vesicular Glycinergic Phenotype
Karin R. Aubrey,1 * Francesco M. Rossi,1,2 * Raquel Ruivo,2 Silvia Alboni,1 Gian Carlo Bellenchi,2 Anne Le Goff,1 Bruno Gasnier,2 andStéphane Supplisson1 1Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique, Ecole Normale Supérieure, 75005 Paris, France, and 2Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1929, Université Paris 7 Denis Diderot, 75005 Paris, France
Correspondence should be addressed to either of the following: B. Gasnier, Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique Unité Propre de Recherche 1929, 13 rue Pierre et Marie Curie, 75005 Paris, France, Email: bruno.gasnier{at}ibpc.fr; or S. Supplisson, Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique, Ecole normale supérieure, 46 rue d'Ulm, 75005 Paris, France, Email: supplis{at}ens.fr
The mechanisms that specify the vesicular phenotype of inhibitory interneurons in vertebrates are poorly understood because the two main inhibitory transmitters, glycine and GABA, share the same vesicular inhibitory amino acid transporter (VIAAT) and are both present in neurons during postnatal development. We have expressed VIAAT and the plasmalemmal transporters for glycine and GABA in a neuroendocrine cell line and measured the quantal release of glycine and GABA using a novel double-sniffer patch-clamp technique. We found that glycine is released from vesicles when VIAAT is coexpressed with either the neuronal transporter GlyT2 or the glial transporter GlyT1. However, GlyT2 was more effective than GlyT1, probably because GlyT2 is unable to operate in the reverse mode, which gives it an advantage in maintaining the high cytosolic glycine concentration required for efficient vesicular loading by VIAAT. The vesicular inhibitory phenotype was gradually altered from glycinergic to GABAergic through mixed events when GABA is introduced into the secretory cell and competes for uptake by VIAAT. Interestingly, the VIAAT ortholog from Caenorhabditis elegans (UNC-47), a species lacking glycine transmission, also supports glycine exocytosis in the presence of GlyT2, and a point mutation of UNC-47 that abolishes GABA transmission in the worm confers glycine specificity. Together, these results suggest that an increased cytosolic availability of glycine in VIAAT-containing terminals was crucial for the emergence of glycinergic transmission in vertebrates.
Key words: inhibitory transmission; glycine; GABA; vesicles; uptake; quanta
Received March 7, 2007; revised April 17, 2007; accepted May 6, 2007.
Correspondence should be addressed to either of the following: B. Gasnier, Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique Unité Propre de Recherche 1929, 13 rue Pierre et Marie Curie, 75005 Paris, France, Email: bruno.gasnier{at}ibpc.fr; or S. Supplisson, Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique, Ecole normale supérieure, 46 rue d'Ulm, 75005 Paris, France, Email: supplis{at}ens.fr
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