H+/myo-inositol transporter genes, hmit-1.1 and hmit-1.2, have roles in the osmoprotective response in Caenorhabditis elegans
H+/myo-inositol transporter genes, hmit-1.1 and hmit-1.2, have roles in the osmoprotective response in Caenorhabditis elegans
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DOI：
10.1016/j.bbrc.2011.06.001
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发表时间：
2011-07-08
影响因子：
3.1
通讯作者：
Mitani, Shohei
中科院分区：
文献类型：
--
作者：
Kage-Nakadai, Eriko;Uehara, Tomoko;Mitani, Shohei
肌醇是脑和肾中的主要有机渗透剂之一。细胞内有机渗压物质的积累允许细胞调节细胞内渗透压而不改变细胞质离子强度，并适应高渗条件。已经鉴定了两种类型的肌醇转运蛋白，钠/肌醇转运蛋白和H+/肌醇转运蛋白（HMIT）。钠/肌醇转运蛋白是渗透胁迫诱导的，可能参与哺乳动物细胞内肌醇的积累。然而，HMIT的作用仍然未知。在本研究中，我们的特点是三个秀丽隐杆线虫HMIT基因，hmit-1.1，hmit-1.2，和hmit-1.3。HMIT-1.1在肠中表达，HMIT-1.2在神经胶质和排泄管中表达，排泄管是功能上类似于肾的渗透调节器官。HMIT-1.3在肠和胶质细胞中表达。在高渗条件下，hmit-1.1和hmit-1.2的表达被显著诱导，但hmit-1.3的表达不被显著诱导。突变型hmit-1.1和hmit-1.2的动物对渗透压应激具有高敏感性。hmit-1.1和hmit-1.2突变体的缺陷分别被hmit-1.1和hmit-1.2转基因以及修饰的人HMIT拯救。在人细胞系中，HMIT表达在高渗条件下诱导。这些结果表明，C。HMIT家族在线虫的保护性反应中起着至关重要的作用。(C)2011 Elsevier Inc. All rights reserved.
Myo-inositol is one of the major organic osmolytes in the brain and the kidney. The accumulation of intracellular organic osmolytes allows cells to regulate intracellular osmolality without altering cytoplasmic ionic strength and to adapt to hyperosmotic conditions. Two types of myo-inositol transporters, sodium/myo-inositol transporter and H+/myo-inositol transporter (HMIT), have been identified. Sodium/myo-inositol transporters are induced by osmotic stress and might be involved in the intracellular accumulation of myo-inositol in mammals. The role of HMIT, however, remains unknown. In the present study, we characterized three Caenorhabditis elegans HMIT genes, hmit-1.1, hmit-1.2, and hmit-1.3. hmit-1.1 was expressed in the intestine, and hmit-1.2 was expressed in the glia and the excretory canal, which is an osmotic regulatory organ that is functionally analogous to the kidney. hmit-1.3 was expressed in the intestine and the glia. The expression of hmit-1.1 and hmit-1.2 but not hmit-1.3, was markedly induced under hyperosmotic conditions. Animals with mutant hmit-1.1 and hmit-1.2 were hypersensitive to osmotic stress. The defects of hmit-1.1 and hmit-1.2 mutants were rescued by hmit-1.1 and hmit-1.2 transgenes, respectively, and by modified human HMIT. In human cell lines, HMIT expression was induced in hyperosmotic conditions. These findings indicate that the C. elegans HMIT family has a crucial role in the osmoprotective response. (C) 2011 Elsevier Inc. All rights reserved.