An ATP Receptor in Tetrahymena

在大多数多细胞生物中，ATP是一种兴奋性神经递质。然而，初步证据表明，甚至在单细胞生物中也发现ATP受体，特别是在纤毛虫四膜虫中。这一证据表明，四膜膜受体通过诱导atp依赖的膜去极化（通过诱导膜钙电导的变化）和动作电位，导致反复的向后和向前游泳，称为“避免反应”，从而作为化学驱避受体。这种行为改变了细胞的方向，使它们能够避免高浓度的ATP，这是一种通常由裂解细胞释放的化合物。这类似于外界ATP在脊椎动物疼痛接受中作为细胞溶解指标的作用。因此，四膜虫的ATP接受可能是高等生物神经传递的进化前体，四膜虫的ATP受体可能与脊椎动物的ATP受体有显著的相似性。这种相似性进一步被一种针对脊椎动物ATP受体亚群（P2X1受体）的抗体与四膜虫的膜蛋白交叉反应的能力所证明。实验将确定这种蛋白质是否是ATP受体，如果是，将确定其特征。免疫沉淀将作为纯化的基础。行为生物分析、电生理学、分子生物学和生物化学技术将被用来验证受体在细胞中的位置并确定其特性。进一步的研究将确定化学感觉适应的生化机制。这项工作将推进化学驱素接受和适应的基础知识，并将为神经递质系统的进化提供见解。该项目还将有助于参与研究的高中生、本科生和研究生的教育。

ATP is an excitatory neurotransmitter in most multicellular organisms. However, preliminary evidence suggests that ATP receptors are found even in unicellular organisms, specifically in the ciliate Tetrahymena. This evidence suggests that the Tetrahymena receptor serves as a chemorepellent receptor by eliciting an ATP-dependent membrane depolarization (by inducing a change in membrane calcium conductance) and action potentials that result in repetitive bouts of backward and forward swimming called "avoiding reactions". This behavior re-orients the cells to enable them to avoid high concentrations of ATP, a compound normally released by lysed cells. This is similar to the proposed role of external ATP as an indicator of cell lysis in pain reception in vertebrates. Thus, ATP reception in Tetrahymena may be an evolutionary precursor to neurotransmission in higher organisms, and the Tetrahymena ATP receptor may have significant similarities to vertebrate ATP receptors. Such a similarity is further suggested by the ability of an antibody made against a subset of vertebrate ATP receptors (P2X1 receptors) to cross-react with a membrane protein of Tetrahymena. Experiments will determine if this protein is the ATP receptor and, if so, to characterize it. Immunoprecipitation will be used as a basis for purification. Behavioral bioassays, and electrophysiological, molecular biological and biochemical techniques will be utilized to verify the location of the receptor in the cell and to determine its properties. Additional studies will determine of the biochemical mechanisms involved in chemosensory adaptation. This work will advance basic knowledge of chemorepellent reception and adaptation, and will provide insights into the evolution of neurotransmitter systems. The project will also contribute towards education of students at the high school, undergraduate and graduate levels who will participate in the research.