The Caenorhabditis elegans snf-11 gene encodes a sodium-dependent GABA transporter required for clearance of synaptic GABA
The Caenorhabditis elegans snf-11 gene encodes a sodium-dependent GABA transporter required for clearance of synaptic GABA
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DOI：
10.1091/mbc.e06-02-0155
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发表时间：
2006-07-01
影响因子：
3.3
通讯作者：
Rand, James B.
中科院分区：
文献类型：
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作者：
Mullen, Gregory P.;Mathews, Eleanor A.;Rand, James B.
依赖钠的神经递质转运蛋白参与突触裂隙中神经递质的清除和/或回收。秀丽隐杆线虫中的SNF-11基因编码与哺乳动物GABA转运蛋白（GAT）高相似的蛋白质。我们在这里显示SNF-11编码功能性GABA转运蛋白； SNF-11介导的GABA转运为Na+且cl-依赖性，EC50值为168 MU M，并被GAT1抑制剂SKF89976A阻塞。 SNF-11蛋白在七个GABA能神经元中表达，头部其他几个神经元和逆转神经节和三组肌肉细胞表达。因此，所有GABA能突触均与SNF-11的突触前或突触后（或两者）相关。尽管SNF-11无效突变对GABA能行为没有明显的影响，但它导致对乙酰胆碱酯酶的抑制剂的抗性。在体内，SNF-11无效突变阻止了至少一部分GABA能细胞中的GABA摄取。在细胞培养系统中，SNF-11突变消除了所有GABA摄取。我们得出的结论是，GABA转运活性对于秀丽隐杆线虫中的正常GABA能功能并不是必不可少的，并且SNF-11的定位与GABA清除功能一致，而不是回收。
Sodium-dependent neurotransmitter transporters participate in the clearance and/or recycling of neurotransmitters from synaptic clefts. The snf-11 gene in Caenorhabditis elegans encodes a protein of high similarity to mammalian GABA transporters (GATs). We show here that snf-11 encodes a functional GABA transporter; SNF-11-mediated GABA transport is Na+ and Cl- dependent, has an EC50 value of 168 mu M, and is blocked by the GAT1 inhibitor SKF89976A. The SNF-11 protein is expressed in seven GABAergic neurons, several additional neurons in the head and retrovesicular ganglion, and three groups of muscle cells. Therefore, all GABAergic synapses are associated with either presynaptic or postsynaptic (or both) expression of SNF-11. Although a snf-11 null mutation has no obvious effects on GABAergic behaviors, it leads to resistance to inhibitors of acetylcholinesterase. In vivo, a snf-11 null mutation blocks GABA uptake in at least a subset of GABAergic cells; in a cell culture system, all GABA uptake is abolished by the snf-11 mutation. We conclude that GABA transport activity is not essential for normal GABAergic function in C. elegans and that the localization of SNF-11 is consistent with a GABA clearance function rather than recycling.