Adams R H, Sato K, Shimada S, Tohyama M, Püschel A W, Betz H
Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt/Main, Germany.
J Neurosci. 1995 Mar;15(3 Pt 2):2524-32. doi: 10.1523/JNEUROSCI.15-03-02524.1995.
Na+/Cl(-)-dependent glycine transporters are crucial for the termination of neurotransmission at glycinergic synapses. Two different glycine transporter genes, GlyT1 and GlyT2, have been described. Several isoforms differing in their 5' ends originate from the GlyT1 gene. We have determined the genomic structure of the murine GlyT1 gene to elucidate the genetic basis underlying the different isoforms. Analysis of cDNA 5'-ends revealed that the GlyT1a and 1b/1c mRNAs are transcribed from two different promoters. During murine embryonic development GlyT1 mRNAs were detectable by RNase protection assays as early as embryonic day E9 and reached maximal levels between E13 and E15. In situ hybridization revealed GlyT1 expression in the developing spinal cord mainly in the ventral part of the ventricular zone at E12. At later stages (E15) transcripts were also found in the lateral half of the basal and intermediate gray matter. In contrast, the second glycine transporter gene GlyT2 displayed a completely different expression pattern. At E11 it is expressed in the mantle zone, and at later stages throughout the ventral horns. In the adult rat brain and spinal cord, GlyT1 hybridization signals were found exclusively in glial cells. Our data indicate that GlyT1 is an early marker of neural development and encodes glia-specific transporter proteins.
钠/氯依赖性甘氨酸转运体对于甘氨酸能突触处神经传递的终止至关重要。已描述了两种不同的甘氨酸转运体基因,即GlyT1和GlyT2。源自GlyT1基因的几种在5'端不同的同工型已被发现。我们确定了小鼠GlyT1基因的基因组结构,以阐明不同同工型的遗传基础。对cDNA 5'端的分析表明,GlyT1a和1b/1c mRNA是从两个不同的启动子转录而来的。在小鼠胚胎发育过程中,通过核糖核酸酶保护试验最早在胚胎第9天就可检测到GlyT1 mRNA,并且在第13天至第15天达到最高水平。原位杂交显示,在胚胎第12天,GlyT1在发育中的脊髓中主要在室带的腹侧部分表达。在后期阶段(第15天),在基底和中间灰质的外侧半部也发现了转录本。相比之下,第二个甘氨酸转运体基因GlyT2表现出完全不同的表达模式。在第11天,它在套层区表达,在后期阶段则在整个腹角表达。在成年大鼠脑和脊髓中,仅在神经胶质细胞中发现了GlyT1杂交信号。我们的数据表明,GlyT1是神经发育的早期标志物,并编码神经胶质细胞特异性转运蛋白。