Characterization of a novel D2-like dopamine receptor with a truncated splice variant and a D1-like dopamine receptor unique to invertebrates from Caenorhabditis elegans
Characterization of a novel D2-like dopamine receptor with a truncated splice variant and a D1-like dopamine receptor unique to invertebrates from Caenorhabditis elegans
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DOI：
10.1111/j.1471-4159.2005.03268.x
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发表时间：
2005-08-01
影响因子：
4.7
通讯作者：
Ishiura, S
中科院分区：
文献类型：
--
作者：
Sugiura, M;Fuke, S;Ishiura, S
我们克隆了两个新的秀丽隐杆线虫多巴胺受体dop3和dop4。dop3与其他d2样多巴胺受体具有高度序列同源性。由于选择性剪接，产生了截断的DOP-3剪接变体DOP-3nf。由于在胞内环的第三个停止密码子的帧内插入，dop3nf缺乏全长dop3受体中发现的第六和第七跨膜结构域。报告基因分析显示，dop3在多巴胺刺激下减弱福斯克林刺激下cAMP的形成，而dop3nf则不然。当dop3与dop3nf共表达时，抑制forskolin刺激的cAMP形成的能力降低。dop4与哺乳类d1样多巴胺受体不同，与无脊椎动物特有的d1样多巴胺受体具有高度序列同源性。报告基因分析表明，dop4在多巴胺刺激下刺激cAMP的积累。这两种受体为在分子水平上理解多巴胺能信号提供了新的机会。
We have cloned two novel Caenorhabditis elegans dopamine receptors, DOP-3 and DOP-4. DOP-3 shows high sequence homology with other D2-like dopamine receptors. As a result of alternative splicing, a truncated splice variant of DOP-3, DOP-3nf, was produced. Because of the in-frame insertion of a stop codon in the third intracellular loop, DOP-3nf lacks the sixth and seventh transmembrane domains that are found in the full-length DOP-3 receptor. Reporter gene assay showed that DOP-3 attenuates forskolin-stimulated cAMP formation in response to dopamine stimulation, whereas DOP-3nf does not. When DOP-3 was coexpressed with DOP-3nf, the ability to inhibit forskolin-stimulated cAMP formation was reduced. DOP-4 shows high sequence homology with D1-like dopamine receptors unique to invertebrates, which are distinct from mammalian D1-like dopamine receptors. Reporter gene assay showed that DOP-4 stimulates cAMP accumulation in response to dopamine stimulation. These two receptors provide new opportunities to understand dopaminergic signaling at the molecular level.