Cellular and molecular mechanisms of epithelial ion transport and excretion in invertebrates

无脊椎动物上皮离子转运和排泄的细胞和分子机制

• 批准号: RGPIN-2015-05359
• 负责人: ODonnell, Michael
• 金额: $ 5.17万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613503
• 关键词: Cellular; molecular; mechanisms; epithelial; ion

All terrestrial animals regulate the concentrations of ions in their cells and body fluids. In addition, they must eliminate wastes and toxins from their bodies. This research examines how transporting epithelia within insects and nematode worms excrete toxins and regulate the levels of water, ions, acids and bases. Some of our experiments on epithelial transport use model organisms, such as fruit flies and the nematode worm C. elegans, because such studies provide information which is relevant to understanding related processes in other organisms, including humans. Epithelia are layers of cells which form a barrier between two compartments, and which transport materials such as inorganic salts (sodium, chloride, etc.) and water between one fluid-filled compartment, often external, and a second internal compartment. Examples of fluids in external compartments include water flowing over the gills of an aquatic species, the contents of the digestive tract, and urine or blood filtrate contained within the excretory system. Examples of fluids in internal compartments include the blood and extracellular fluids which transport nutrients to, or from, the gut and excretory system. The activities of epithelia which secrete or reabsorb ions, nutrients, waste materials, toxins or water from particular compartments can be controlled by hormones released into the circulatory system. The hormones bind to receptors in cell membranes and activate intracellular second messenger systems. This cascade of cell signaling often leads to activation of membrane proteins which transport particular ions. Research into the mechanisms and control of transporting epithelia in insects and nematodes provides three benefits: 1) Knowledge of the cellular mechanisms and hormonal control of transporting epithelia in pest species of insect facilitates rational design of novel and environmentally benign control measures. For example, understanding the mechanisms of excretion of toxic materials by epithelia aids development of compounds which block such excretion in pest insects. 2) Understanding the mechanisms of transporting epithelia is central to understanding how insects and nematodes adapt to different environments, and how natural or man-made changes (e.g. environmental pollution) may have deleterious effects on these and other animals. 3) Epithelial tissues of insects and nematodes provide useful model systems for understanding the cellular mechanisms of excretion and ion transport. The use of genetically well-characterized species, such as fruit flies and nematode worms, allows us to examine the effects of mutations or knockouts of genes controlling the expression of specific membrane transporters. Such studies help us to learn the roles of similar genes in other animals, including humans, and can thus contribute to understanding the basis of diseases in tissues such as the gut and the kidney.

所有陆生动物都调节其细胞和体液中的离子浓度。此外，他们必须排除体内的废物和毒素。本研究探讨了昆虫和线虫蠕虫的运输上皮细胞如何分泌毒素并调节水、离子、酸和碱的水平。我们的一些关于上皮转运的实验使用了模式生物，如果蝇和线虫C。因为这些研究提供了与理解包括人类在内的其他生物体的相关过程相关的信息。上皮是在两个隔室之间形成屏障的细胞层，并且其运输诸如无机盐（钠、氯化物等）的物质。以及水在一个流体填充隔室（通常是外部隔室）和第二内部隔室之间。外部隔室中的流体的实例包括流过水生物种的鳃的水、消化道的内容物以及排泄系统内包含的尿液或血液滤液。内部隔室中的流体的实例包括血液和细胞外液，其将营养物运输到肠道和排泄系统或从肠道和排泄系统运输营养物。上皮细胞分泌或再吸收离子、营养物、废物、毒素或来自特定隔室的水的活动可以通过释放到循环系统中的激素来控制。这些激素与细胞膜上的受体结合并激活细胞内第二信使系统。这种级联的细胞信号传导常常导致转运特定离子的膜蛋白的激活。对昆虫和线虫中上皮细胞转运机制和调控的研究提供了三个益处：1）了解昆虫害虫中上皮细胞转运的细胞机制和激素调控有助于合理设计新颖的和环境友好的控制措施。例如，了解上皮细胞排泄有毒物质的机制有助于开发在害虫中阻断这种排泄的化合物。2)了解运输上皮细胞的机制对于了解昆虫和线虫如何适应不同的环境以及自然或人为变化（例如环境污染）如何对这些和其他动物产生有害影响至关重要。3)昆虫和线虫的上皮组织为理解排泄和离子转运的细胞机制提供了有用的模型系统。使用遗传特征良好的物种，如果蝇和蠕虫使我们能够检查控制特定膜转运蛋白表达的基因突变或敲除的影响。这些研究有助于我们了解类似基因在包括人类在内的其他动物中的作用，从而有助于理解肠道和肾脏等组织疾病的基础。