The Drosophila inebriated-encoded neurotransmitter/osmolyte transporter: dual roles in the control of neuronal excitability and the osmotic stress response.
The Drosophila inebriated-encoded neurotransmitter/osmolyte transporter: dual roles in the control of neuronal excitability and the osmotic stress response.
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果蝇醉酒编码的神经递质/渗透剂转运蛋白：在控制神经元兴奋性和渗透应激反应中的双重作用。
DOI：
10.1093/genetics/160.2.561
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发表时间：
2002
期刊：
影响因子：
3.3
通讯作者：
Stern,Michael
中科院分区：
文献类型：
--
作者：
Huang,Xi;Huang,Yanmei;Chinnappan,Raj;Bocchini,Claire;Gustin,MichaelC;Stern,Michael
哺乳动物肾脏和昆虫马氏小管/后肠等器官的水重吸收需要器官内有一个高渗区域。为了平衡高细胞外渗透压，这些区域内的细胞积累称为渗透剂的有机小分子。这些渗透剂可以积累到高水平，而不会对细胞过程产生毒性作用。在这里，我们提供的证据与以下可能性一致：theinebriated(ine) 基因编码的两种蛋白质异构体是 Na+/Cl− 依赖性神经递质/渗透剂转运蛋白家族的成员，在马氏小管和后肠内执行渗透剂转运。我们表明，缺乏这两种同工型的突变体对渗透压过敏，我们通过将果蝇维持在含有 NaCl、KCl 或山梨醇的培养基上进行测定，并且这种超敏反应可以通过茶氨酸-RB同工型的高水平异位表达完全挽救。我们提供的证据表明，这种超敏反应代表了一种与ine突变体的神经元兴奋性增加表型不同的作用。最后，我们表明每种基因型都表现出一个“阈值”[NaCl]：在含 NaCl 的培养基上长期维持在高于而不是低于阈值的水平会导致致死。此外，该阈值随着不活动量的增加而增加。这些数据表明，基因突变通过防止马氏小管和后肠内渗透物的积累而赋予渗透应激敏感性。
Water reabsorption by organs such as the mammalian kidney and insect Malpighian tubule/hindgut requires a region of hypertonicity within the organ. To balance the high extracellular osmolarity, cells within these regions accumulate small organic molecules called osmolytes. These osmolytes can accumulate to a high level without toxic effects on cellular processes. Here we provide evidence consistent with the possibility that the two protein isoforms encoded by theinebriated(ine) gene, which are members of the Na+/Cl−-dependent neurotransmitter/osmolyte transporter family, perform osmolyte transport within the Malpighian tubule and hindgut. We show thatinemutants lacking both isoforms are hypersensitive to osmotic stress, which we assayed by maintaining flies on media containing NaCl, KCl, or sorbitol, and that this hypersensitivity is completely rescued by high-level ectopic expression of theine-RBisoform. We provide evidence that this hypersensitivity represents a role forinethat is distinct from the increased neuronal excitability phenotype ofinemutants. Finally, we show that eachinegenotype exhibits a “threshold” [NaCl]: long-term maintenance on NaCl-containing media above, but not below, the threshold causes lethality. Furthermore, this threshold value increases with the amount ofineactivity. These data suggest thatinemutations confer osmotic stress sensitivity by preventing osmolyte accumulation within the Malpighian tubule and hindgut.