An intracellular P2X receptor required for osmoregulation in Dictyostelium discoideum.
An intracellular P2X receptor required for osmoregulation in Dictyostelium discoideum.
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DOI：
10.1038/nature05926
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发表时间：
2007-07-12
期刊：
影响因子：
64.8
通讯作者：
North, R. Alan
中科院分区：
文献类型：
--
作者：
Fountain, Samuel J.;Parkinson, Katie;Young, Mark T.;Cao, Lishuang;Thompson, Christopher R. L.;North, R. Alan
P2 X受体是由细胞外ATP门控的膜离子通道，广泛存在于脊椎动物中，但以前在微生物中没有发现。在这里，我们确定了一个弱相关的基因在社会变形虫Dictyosteelium discoideum的基因组中，并显示，在人类胚胎肾细胞中的异源表达的使用，它编码一个膜离子通道激活ATP（30-100 μM）。定点突变揭示了与高等生物P2 X受体的结构-功能关系的基本保守性。该受体对通常的P2 X拮抗剂不敏感，但被纳摩尔浓度的Cu 2+离子阻断。In D. discoideum中，受体被发现在细胞内膜上，具有显著的定位于细胞调节细胞器，收缩泡。对D. discoideum导致细胞在低渗条件下无法调节细胞体积。在这些突变体细胞的细胞肿胀伴随着一个显着的抑制收缩空泡排空。这些研究结果表明，P2 X受体在细胞内细胞器上的新功能作用，在这种情况下，P2 X调节。
P2X receptors are membrane ion channels gated by extracellular ATP that are found widely in vertebrates, but not previously in microbes. Here we identify a weakly related gene in the genome of the social amoeba Dictyostelium discoideum, and show, with the use of heterologous expression in human embryonic kidney cells, that it encodes a membrane ion channel activated by ATP (30–100 μM). Site-directed mutagenesis revealed essential conservation of structure–function relations with P2X receptors of higher organisms. The receptor was insensitive to the usual P2X antagonists but was blocked by nanomolar concentrations of Cu2+ ions. In D. discoideum, the receptor was found on intracellular membranes, with prominent localization to an osmoregulatory organelle, the contractile vacuole. Targeted disruption of the gene in D. discoideum resulted in cells that were unable to regulate cell volume in hypotonic conditions. Cell swelling in these mutant cells was accompanied by a marked inhibition of contractile vacuole emptying. These findings demonstrate a new functional role for P2X receptors on intracellular organelles, in this case in osmoregulation.
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