A novel glycine receptor alpha Z1 subunit variant in the zebrafish brain.
Alpha subunits of the inhibitory glycine receptor (GlyR) display genetic heterogeneity in mammals and zebrafish. This diversity is increased in mammals by the alternative splicing mechanism. We report here in zebrafish, the characterization of a new alphaZ1 subunit likely arising from alphaZ1 gene by an alternative splice process (alphaZ1L). This novel cDNA possesses 45 supplementary nucleotides at the putative exon2/exon3 boundary. The corresponding protein contains 15 additional amino acids in the NH2-terminal domain. Heterologous expression of homomeric GlyRalphaZ1L in human embryonic kidney-293 cells generates glycine-gated strychnine-sensitive chloride channels with no obvious discrepancy with pharmacological properties of GlyRalphaZ1. Moreover, zinc modulation of glycine-induced currents is identical in alphaZ1 and alphaZ1L glycine receptors. During ontogenesis, simultaneous alphaZ1 and alphaZ1L mRNA synthesis have been observed. Embryonic and adult alphaZ1 and alphaZ1L mRNA expressions are restricted to the CNS. Embryonic alphaZ1L mRNA anatomical pattern of expression is, however, highly restrained and strictly limited to the rostral part of the brain revealing a highly regionalized function of alphaZ1L in the CNS. This report contributes to the characterization of the diversity of glycine receptor isoforms in zebrafish and emphasizes the common mechanism used among vertebrates for creating GlyR variety and specificity.
Devignot
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Laboratoire de Biologie Cellulaire et Moléculaire du Neurone, Institut National de la Santé et de la Recherche Médicale U261, Département des Biotechnologies, Institut Pasteur, 25 rue du Dr Roux, F-75724 Paris, France.
Prado de Carvalho
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Bregestovski
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Goblet
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C
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D009928:Organ Specificity / Q000235:genetics; D021122:Protein Subunits / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D018009:Receptors, Glycine / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology
D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D018009:Receptors, Glycine; D029961:Zebrafish Proteins; D005998:Glycine