Characterization of the brain-enriched Na+/H+ exchanger NHE5

脑富集 Na /H 交换器 NHE5 的表征

• 批准号: 371665-2009
• 负责人: Numata, Masayuki
• 金额: $ 2.7万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=498150
• 关键词: Characterization; brain; enriched; Na+; H+

Maintenance of the cellular acidity (pH) is important for most cell types as the majority of biochemical reactions and protein structures are tightly regulated by pH within the physiological range. This is especially the case with nerve cells (neurons) that conduct nerve impulses. In addition to the fundamental roles commonly observed in various cell types, highly localized and transient pH regulation mechanisms play crucial roles in modulating neuronal activities. For example, pH shifts modulate excitability because the function of many ion channels that are responsible for creating and conveying electric stimuli along the neuron is substantially influenced by changes in pH. Electric stimuli at the specialized structure located close to the adjacent neuron stimulate to release chemical substances called "neurotransmitters". This is sensed by "receptors" that bind to and react with the neurotransmitter. Release of neurotransmitters and recognition by the receptor allow neurons to transmit signals from one neuron to another. Neuronal pH regulates both release of neurotransmitters and proper function of receptors. Not surprisingly, neurons possess a number of sophisticated mechanisms to regulate cellular pH. Among them, Na+/H+ exchangers (NHEs), a group of ion transporters that exchange Na+ for H+ across membranes are proposed to be one of the most prominent players. This notion was strongly supported by the previous finding that genetic depletion of an NHE gene that is expressed in most cell types (NHE1) show brain damage leading to seizures and neuronal cell death. Interestingly, among nine additional NHEs that share similar structure and function, NHE5 is abundantly expressed in brain. Our research group has shown previously that NHE5 has a number of unique characters different from that of NHE1. The unique feature of NHE5 may account for novel roles in brain. We will test our hypothesis in which NHE5 regulates neuronal function and neuronal development by using various model cell systems. Our research will help advance basic knowledge in our understanding of pH regulation in neurons and aim to determine its impact on brain functions such as learning and memory.

细胞酸度（pH）的维持对于大多数细胞类型是重要的，因为大多数生化反应和蛋白质结构在生理范围内受到pH的严格调节。 传导神经冲动的神经细胞（神经元）尤其如此。 除了在各种细胞类型中通常观察到的基本作用之外，高度局部化和瞬时pH调节机制在调节神经元活动中起关键作用。 例如，pH变化调节兴奋性，因为负责沿神经元沿着产生和传递电刺激的许多离子通道的功能基本上受到pH变化的影响。位于邻近神经元附近的专门结构处的电刺激刺激释放称为“神经递质”的化学物质。 这是由“受体”感觉到的，受体与神经递质结合并起反应。 神经递质的释放和受体的识别允许神经元将信号从一个神经元传递到另一个神经元。 神经元pH调节神经递质的释放和受体的正常功能。 毫不奇怪，神经元具有许多复杂的机制来调节细胞的pH值。其中，Na+/H+交换器（NHE），一组离子转运蛋白，交换Na+为H+跨膜被认为是最突出的球员之一。 这一观点得到了先前发现的有力支持，即在大多数细胞类型中表达的NHE基因（NHE 1）的遗传缺失显示脑损伤导致癫痫发作和神经元细胞死亡。 有趣的是，在另外9个具有相似结构和功能的NHE中，NHE 5在大脑中大量表达。 我们的研究小组先前已经表明，NHE 5具有许多不同于NHE 1的独特特征。 NHE 5的独特功能可能解释了其在脑中的新作用。 我们将测试我们的假设，其中NHE 5调节神经元的功能和神经元的发育，通过使用各种模型细胞系统。 我们的研究将有助于推进我们对神经元pH调节的理解，并旨在确定其对学习和记忆等大脑功能的影响。