The molecular basis for calcium release by NAADP

身体的所有细胞都用一层膜从物理上与周围环境隔开。为了让细胞对血液中的因素(如激素)做出反应，这些因素通常不能通过细胞膜，因此使用了特殊的信使分子，这些分子在刺激与细胞接触时在细胞内产生。NAADP是其中一种分子，它通过调节钙离子浓度的变化来控制细胞功能。这些钙的变化对许多过程都很重要，例如，受精。了解NAADP如何增加钙水平对于了解细胞如何工作很重要，但目前我们不知道响应NAADP而打开的允许钙水平变化的蛋白质或‘通道’的身份。在这个计划中，我们将研究一个我们知之甚少但我们最初的实验表明是NAADP通道的蛋白质家族。我们将确定它们在细胞内的位置，确定它们对NAADP的确切反应，以及它们是否需要使NAADP介导钙变化的激素。我们的实验结果将为NAADP如何发挥作用提供迫切需要的信息，并为进一步研究NAADP的影响提供实验工具。

All cells of the body are physically separated from their surrounding environment by a membrane. In order for cells to respond to factors in the blood (such as hormones) which normally can not pass through the membrane, special 'messenger' molecules are used that are generated inside the cell upon contact of the stimulus with the cell. One of these molecules, NAADP controls cell function by mediating changes in the concentration of calcium. These calcium changes are important for many processes including, for example, fertilisation. Understanding how NAADP increases calcium levels is important to understand how cells work but at present we do not know the identity of the protein or 'channel' that opens in response to NAADP to allow calcium levels to change. In this proposal, we will study a family of proteins that we know very little about but which our initial experiments suggest are the channels for NAADP. We will define their location within the cell, determine exactly how they respond to NAADP and whether they are needed for hormones which make NAADP to mediate changes in calcium. The results of our experiments will provide urgently needed information on how NAADP functions and experimental tools to further study the effects of NAADP.