Molecular cloning and functional expression of the human glycine transporter GlyT2 and chromosomal localisation of the gene in the human genome

被引:63
作者
Morrow, JA [1 ]
Collie, IT [1 ]
Dunbar, DR [1 ]
Walker, GB [1 ]
Shahid, M [1 ]
Hill, DR [1 ]
机构
[1] Organon Labs Ltd, Target Discovery Sect, Newhouse ML1 5SH, Lanark, Scotland
关键词
glycine transporter; cDNA cloning; genomic localization; neurotransmitter; human spinal cord; brain stem; cerebellum;
D O I
10.1016/S0014-5793(98)01390-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neurotransmitter transport systems are major targets for therapeutic alterations in synaptic function. We ha ce cloned and sequenced a cDNA encoding the human type 2 glycine transporter GlyT2 from human brain and spinal cord. An open reading frame of 2391 nucleotides encodes a 797 amino acid protein that transports glycine in a Na+/Cl--dependent manner. When stably expressed in CHO cells, human GlyT2 displays a dose-dependent uptake of glycine with an apparent K-m of 108 mu M. This uptake is not affected by sarcosine at concentrations up to 1 mM. Radiation hybrid analysis mapped the GlyT2 gene to D11S1308 (LOD = 8.988) on human chromosome 11p15.1-15.2. (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:334 / 340
页数:7
相关论文
共 53 条
  • [1] GENE STRUCTURE AND GLIAL EXPRESSION OF THE GLYCINE TRANSPORTER GLYT1 IN EMBRYONIC AND ADULT RODENTS
    ADAMS, RH
    SATO, K
    SHIMADA, S
    TOHYAMA, M
    PUSCHEL, AW
    BETZ, H
    [J]. JOURNAL OF NEUROSCIENCE, 1995, 15 (03) : 2524 - 2532
  • [2] Aprison M. H., 1990, GLYCINE NEUROTRANSMI, P1
  • [3] ARRIZA JL, 1993, J BIOL CHEM, V268, P15329
  • [4] CLONING AND EXPRESSION OF A FUNCTIONAL SEROTONIN TRANSPORTER FROM RAT-BRAIN
    BLAKELY, RD
    BERSON, HE
    FREMEAU, RT
    CARON, MG
    PEEK, MM
    PRINCE, HK
    BRADLEY, CC
    [J]. NATURE, 1991, 354 (6348) : 66 - 70
  • [5] BORDEN LA, 1992, J BIOL CHEM, V267, P21098
  • [6] 2 GLYCINE TRANSPORTER VARIANTS WITH DISTINCT LOCALIZATION IN THE CNS AND PERIPHERAL-TISSUES ARE ENCODED BY A COMMON GENE
    BOROWSKY, B
    MEZEY, E
    HOFFMAN, BJ
    [J]. NEURON, 1993, 10 (05) : 851 - 863
  • [7] ROLE OF SYSTEM GLY IN GLYCINE TRANSPORT IN MONOLAYER-CULTURES OF LIVER-CELLS
    CHRISTENSEN, HN
    HANDLOGTEN, ME
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1981, 98 (01) : 102 - 107
  • [8] FUNCTIONAL EXPRESSION AND CNS DISTRIBUTION OF A BETA-ALANINE-SENSITIVE NEURONAL GABA TRANSPORTER
    CLARK, JA
    DEUTCH, AY
    GALLIPOLI, PZ
    AMARA, SG
    [J]. NEURON, 1992, 9 (02) : 337 - 348
  • [9] AN EXCITATORY AMINO-ACID TRANSPORTER WITH PROPERTIES OF A LIGAND-GATED CHLORIDE CHANNEL
    FAIRMAN, WA
    VANDENBERG, RJ
    ARRIZA, JL
    KAVANAUGH, MP
    AMARA, SG
    [J]. NATURE, 1995, 375 (6532) : 599 - 603
  • [10] MOLECULAR-CLONING AND EXPRESSION OF A HIGH-AFFINITY L-PROLINE TRANSPORTER EXPRESSED IN PUTATIVE GLUTAMATERGIC PATHWAYS OF RAT-BRAIN
    FREMEAU, RT
    CARON, MG
    BLAKELY, RD
    [J]. NEURON, 1992, 8 (05) : 915 - 926