The orphan pentameric ligand-gated ion channel pHCl-2 is gated by pH and regulates fluid secretion in Drosophila Malpighian tubules
The orphan pentameric ligand-gated ion channel pHCl-2 is gated by pH and regulates fluid secretion in Drosophila Malpighian tubules
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DOI：
10.1242/jeb.141069
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发表时间：
2016-09-01
影响因子：
2.8
通讯作者：
Dent, Joseph A.
中科院分区：
文献类型：
--
作者：
Feingold, Daniel;Starc, Tanja;Dent, Joseph A.
五聚体配体门控离子通道（pLGICs）是后生动物中一个庞大的蛋白质超家族，其作为神经递质受体介导快速的亲离子性突触传递已被广泛研究。虽然绝大多数pLGIC似乎是神经递质受体，但在非神经元组织中的pLGIC和原核生物中的同源pLGIC样蛋白的鉴定指出了独立于神经元信号传导的生物学功能，可能是祖先的。在这里，我们报告的分子和生理特性的高度分歧，孤儿pLGIC亚基编码的pHCl-2（CG 11340）基因，在果蝇。我们发现，pHCl-2形成一个通道，是不敏感的广泛的神经递质，但相反，门控细胞外pH值的变化。pHCl-2的表达在马氏管，这是非神经支配的肾型分泌组织。我们证明，pHCl-2是本地化的肾小管上皮细胞的主细胞的顶膜和pHCl-2的损失减少排尿过程中的尿产量。我们的数据暗示pHCl-2作为适当的尿液产生所需的氯离子电导的重要来源，突出了pLGIC在上皮组织中调节液体分泌和渗透稳态的新作用。
Pentameric ligand-gated ion channels (pLGICs) constitute a large protein superfamily in metazoa whose role as neurotransmitter receptors mediating rapid, ionotropic synaptic transmission has been extensively studied. Although the vast majority of pLGICs appear to be neurotransmitter receptors, the identification of pLGICs in non-neuronal tissues and homologous pLGIC-like proteins in prokaryotes points to biological functions, possibly ancestral, that are independent of neuronal signalling. Here, we report the molecular and physiological characterization of a highly divergent, orphan pLGIC subunit encoded by the pHCl-2 (CG11340) gene, in Drosophila melanogaster. We show that pHCl-2 forms a channel that is insensitive to a wide array of neurotransmitters, but is instead gated by changes in extracellular pH. pHCl-2 is expressed in the Malpighian tubules, which are non-innervated renal-type secretory tissues. We demonstrate that pHCl-2 is localized to the apical membrane of the epithelial principal cells of the tubules and that loss of pHCl-2 reduces urine production during diuresis. Our data implicate pHCl-2 as an important source of chloride conductance required for proper urine production, highlighting a novel role for pLGICs in epithelial tissues regulating fluid secretion and osmotic homeostasis.