Liu Q R, López-Corcuera B, Mandiyan S, Nelson H, Nelson N
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110.
J Biol Chem. 1993 Oct 25;268(30):22802-8.
A novel glycine transporter (GLYT2) was cloned from a rat brain cDNA library. GLYT2 is about 48 and 50% homologous to the previously cloned mouse glycine transporter (GLYT1) and rat proline transporter (PROT), respectively. GLYT2 differs from GLYT1 in molecular structure, tissue specificity, and pharmacological properties. The cDNA of GLYT2 encodes for 799 amino acid residues with an extended amino-terminal peptide containing 200 amino acids before the first transmembrane domain. Potential phosphorylation sites for protein kinase C, cAMP-dependent kinase, and calmodulin-dependent kinase were identified in the amino-terminal region. GLYT2 mRNA was shown to be specifically localized in spinal cord, brain stem, and to a lesser extent in the cerebellum. In contrast, GLYT1 mRNA distribution in the brain has been found previously to be more ubiquitous. Xenopus oocytes injected with GLYT2 cRNA transport glycine with a Km of 17 microM, and the uptake of glycine is resistant to inhibition by sarcosine. The experimental data suggests GLYT2 might play a major role in the termination of the inhibitory effect of glycine in the brain stem and spinal cord of vertebrates. On the other hand, the main function of GLYT1 may be in the modulation of excitatory nerve terminals. Two types of GLYT1 cDNA, GLYT1a and GLYT1b, were cloned from the mouse brain library. They differ only at their amino-terminal sequences, and GLYT1b contains two additional potential phosphorylation sites for proline-dependent kinase. Cloning of the gene encoding the GLYT1 revealed that the two variants resulted from a differential splicing.
一种新型甘氨酸转运体（GLYT2）是从大鼠脑cDNA文库中克隆得到的。GLYT2与先前克隆的小鼠甘氨酸转运体（GLYT1）和大鼠脯氨酸转运体（PROT）的同源性分别约为48%和50%。GLYT2在分子结构、组织特异性和药理学特性方面与GLYT1不同。GLYT2的cDNA编码799个氨基酸残基，在第一个跨膜结构域之前有一个包含200个氨基酸的延长氨基末端肽。在氨基末端区域鉴定出了蛋白激酶C、cAMP依赖性激酶和钙调蛋白依赖性激酶的潜在磷酸化位点。已证明GLYT2 mRNA特异性定位于脊髓、脑干，在小脑中有较少程度的定位。相比之下，先前发现GLYT1 mRNA在脑中的分布更为广泛。注射GLYT2 cRNA的非洲爪蟾卵母细胞转运甘氨酸的Km值为17 microM，甘氨酸的摄取对肌氨酸的抑制具有抗性。实验数据表明，GLYT2可能在脊椎动物脑干和脊髓中甘氨酸抑制作用的终止中起主要作用。另一方面，GLYT1的主要功能可能在于调节兴奋性神经末梢。从小鼠脑文库中克隆出了两种类型的GLYT1 cDNA（GLYT1a和GLYT1b）。它们仅在氨基末端序列上有所不同，并且GLYT1b含有两个额外的脯氨酸依赖性激酶潜在磷酸化位点。编码GLYT1的基因克隆表明，这两种变体源自差异剪接。
