Modulation of Calcium Signaling in Neurons

神经细胞将电信号转化为钙离子的变化，从而引发生化反应。只有在刺激或病理条件下，钙水平才会升高。在正常情况下，通过一系列复杂的途径将钙泵出细胞或进入细胞器，细胞内钙浓度保持在很低的水平。本研究的目的是研究嵌入细胞膜的钙泵被调节的三种机制。激酶是调节许多细胞过程的信号蛋白。一种名为Lyk的激酶调节钙泵的可能性将被测试。钙泵的Lyk调节将确定神经细胞中激酶和钙信号通路之间的一个新的交叉点。在对有毒刺激的反应中，钙泵从细胞表面移动到细胞膜内。泵贩运的机制将被确定，以提供洞察神经元如何适应压力。3)神经细胞表达钙泵的多种基因变异。某些变异专门调节触发神经递质释放的钙的可能性，这是神经元之间化学通讯的基础，将被研究。为了实现这些目标，神经元将在培养皿中生长，并使用光学和电生理仪器单独研究。在大学环境中开展这个项目为培养科学家创造了一个环境。本科生和博士生预科生、博士后实习生和休假教师都为这项研究做出了贡献，并将继续参与这项研究。钙作为细胞内信使，触发从基因表达到神经递质和激素释放的过程。因此，钙的波动触发神经元的适应性变化，并在细胞间通讯中发挥重要作用。这项工作将增加我们对神经元如何在分子和细胞水平上处理信息的理解。

Nerve cells convert electrical signals into changes in calcium ion to trigger biochemical responses. Only during stimulation or under pathological conditions are calcium levels elevated. Under normal conditions the intracellular calcium concentration is kept very low by a complex series of pathways that pump calcium out of the cell or into organelles. The objective of this proposal is to study three mechanisms by which calcium pumps embedded in the cell-surface membrane are modulated. 1) Kinases are signaling proteins that regulate many cell processes. The possibility that a kinase called Lyk modulates calcium pumps will be tested. Lyk modulation of calcium pumps would identify a novel point of cross-talk between the kinase and calcium signaling pathways in nerve cells. 2) In response to toxic stimuli, calcium pumps move from cell-surface to intracellular membranes. The mechanism of pump trafficking will be determined to provide insight into how neurons adapt to stress. 3) Nerve cells express multiple genetic variants of calcium pumps. The possibility that certain variants specialize in regulating the calcium that triggers neurotransmitter release, the basis for chemical communication between neurons, will be examined. To achieve these goals, neurons will be grown in culture (in a dish) and studied individually with optical and electrophysiological instrumentation.Carrying out this project in a university setting creates an environment for training scientists. Undergraduate and predoctoral students, postdoctoral trainees and faculty on sabbatical leave have all contributed to and will continue to participate in this research.Calcium acts as an intracellular messenger that triggers processes ranging from gene expression to the release of neurotransmitters and hormones. Thus, fluctuations in calcium trigger adaptive changes in neurons and play an essential role in cell-to-cell communication. This work will increase our understanding of how neurons process information at the molecular and cellular level.