A novel glycine receptor αZ1 subunit variant in the zebrafish brain

被引:10
作者
Devignot, V [1 ]
De Carvalho, LP [1 ]
Bregestovski, P [1 ]
Goblet, C [1 ]
机构
[1] Inst Pasteur, Dept Biotechnol, INSERM, Lab Biol Cellulaire & Mol Neurone,U 261, F-75724 Paris, France
关键词
alternative splicing; heterologous expression; ionic currents; zinc modulation; developmental profile; hybridization in situ;
D O I
10.1016/S0306-4522(03)00171-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:449 / 457
页数:9
相关论文
共 48 条
[1]   CLONING OF A GLYCINE RECEPTOR SUBTYPE EXPRESSED IN RAT-BRAIN AND SPINAL-CORD DURING A SPECIFIC PERIOD OF NEURONAL DEVELOPMENT [J].
AKAGI, H ;
HIRAI, K ;
HISHINUMA, F .
FEBS LETTERS, 1991, 281 (1-2) :160-166
[2]   Structure and functions of inhibitory and excitatory glycine receptors [J].
Betz, H ;
Kuhse, J ;
Schmieden, V ;
Laube, B ;
Kirsch, J ;
Harvey, RJ .
MOLECULAR AND FUNCTIONAL DIVERSITY OF ION CHANNELS AND RECEPTORS, 1999, 868 :667-676
[3]   Molecular diversity of GABA-gated chloride channels in the rat anterior pituitary [J].
BoueGrabot, E ;
Dufy, B ;
Garret, M .
BRAIN RESEARCH, 1995, 704 (01) :125-129
[4]  
Breitinger HG, 1998, CURR PHARM DESIGN, V4, P315
[5]   ACTIVATION OF GABA(RHO-1) RECEPTORS BY GLYCINE AND BETA-ALANINE [J].
CALVO, DJ ;
MILEDI, R .
NEUROREPORT, 1995, 6 (08) :1118-1120
[6]   HIGH-EFFICIENCY TRANSFORMATION OF MAMMALIAN-CELLS BY PLASMID DNA [J].
CHEN, C ;
OKAYAMA, H .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (08) :2745-2752
[7]   Cloning, expression and electrophysiological characterization of glycine receptor alpha subunit from zebrafish [J].
David-Watine, B ;
Goblet, C ;
De Saint Jan, D ;
Fucile, S ;
Devignot, V ;
Bregestovski, P ;
Korn, H .
NEUROSCIENCE, 1999, 90 (01) :303-317
[8]  
DESAINTJAN D, 2001, J PHYSL, V353, P741
[9]   RAPID PRODUCTION OF FULL-LENGTH CDNAS FROM RARE TRANSCRIPTS - AMPLIFICATION USING A SINGLE GENE-SPECIFIC OLIGONUCLEOTIDE PRIMER [J].
FROHMAN, MA ;
DUSH, MK ;
MARTIN, GR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (23) :8998-9002
[10]   Comparison of glycine and GABA actions on the zebrafish homomeric glycine receptor [J].
Fucile, S ;
de Saint Jan, D ;
David-Watine, B ;
Korn, H ;
Bregestovski, P .
JOURNAL OF PHYSIOLOGY-LONDON, 1999, 517 (02) :369-383