RUI: The role of Rhesus proteins in Agnathan fishes as a mechanism of ammonia excretion

氨是一种含氮废物，是蛋白质分解的结果，如果任其积累，它是剧毒的，因此许多水生生物已经发展出一种机制，可以在氨产生后立即清除体内的氨。最近，一个膜蛋白家族，恒河（Rh）糖蛋白已被证明具有在高等脊椎动物中运输氨的能力。Rh糖蛋白已在广泛的生物体中被发现，这表明它们具有悠久的进化史。许多关键的生理过程都是基于膜蛋白的功能，这是本提案的重点。由于这些蛋白质可能在基础脊椎动物中以一种独特的方式进化，相对于高等脊椎动物，这个项目有可能回答脊椎动物中不同氨运输模式进化的基本问题。此外，基础脊椎动物（无颌鱼类：盲鳗和七鳃鳗）耐受各种内部和环境氨浓度的独特能力，将使我们能够回答有关氨运输控制和相关膜蛋白可塑性的基本问题。此外，我们希望更清楚地了解为什么盲鳗和七鳃鳗作为唯一幸存的基础脊椎动物Agnatha类成员持续存在了5亿年以上。本提案的目标是：(i)了解盲鳗和海七鳃鳗排泄氨的机制；（ii）量化Rh糖蛋白对盲鳗和七鳃鳗总氨排泄的贡献；确定生命阶段如何改变七鳃鳗的氨排泄；（四）确定七鳃鳗从淡水向海水过渡对氨排泄机制的影响。该项目的教育成果包括许多本科生和研究生参与这项研究。学生将获得体内生理学、分子生物学、蛋白质生物化学和组织学技术方面的经验。学生将参与以团队为基础的伙伴关系，通过这种伙伴关系，他们将获得关键的人际关系、组织技能和对他们的研究的国际视野。

Ammonia is a nitrogenous waste product that results from the breakdown of proteins, if allowed to accumulate it is highly toxic and therefore many aquatic organisms have developed mechanisms to rid their bodies of ammonia as soon as it is produced. Recently a family of membrane proteins, the Rhesus (Rh) glycoproteins has been shown to have the ability to transport ammonia in higher vertebrates. The Rh glycoproteins have been identified in a wide range of organisms and this suggests they have a long evolutionary history. Many key physiological processes are based on the functions of the membrane proteins that are the focus of this proposal. Since those proteins may have evolved in a unique way in the basal vertebrates, relative to higher vertebrates, this project has the potential to answer fundamental questions on the evolution of different modes of ammonia transport in vertebrates. In addition, the unique ability of the basal vertebrates (the jawless fishes: hagfishes and lampreys) to tolerate a wide range of internal and environmental ammonia concentrations, will enable us to answer fundamental questions regarding the control of ammonia transport and the plasticity of membrane proteins involved. In addition, we would like to develop a clearer insight into the factors explaining why hagfishes and lampreys have persisted for over 500 million years as the only surviving members of the basal vertebrate class Agnatha. The objectives for this proposal are to (i) Understand the mechanism(s) of ammonia excretion by hagfish and sea lamprey; (ii) Quantify the contribution that Rh glycoproteins make to overall ammonia excretion in both hagfishes and lampreys; (iii) Ascertain how life stage alters ammonia excretion in the lampreys; (iv) Determine how mechanisms of ammonia excretion are influenced by the fresh water to sea water transition in lampreys. The educational outcomes of this project include involvement of many undergraduate and graduate students in this research. The students will gain experience in in vivo physiology, molecular biology, protein biochemistry and histological techniques. Students will be engaged in team-based partnerships through which they will gain key interpersonal, organizational skills and an international perspective on their research.