The molecular basis for calcium release by NAADP

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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.