NAADP SIGNALING IN MAMMALIAN SYSTEMS

描述：(改编自申请者摘要)本申请表为 对高风险/高影响研究的计划公告的回应。 拟议研究的目标是确定尼古丁 腺嘌呤二核苷酸磷酸(NAADP)是钙的一种介体 哺乳动物系统中的动员。NAADP是β-氨基丁酸的代谢物。 烟酰胺腺嘌呤二核苷酸2‘-磷酸(β-NADP) 发现可以从海胆卵的细胞内储存中动员钙。 这是通过一种不同于IP3或循环调节的机制来实现的 ADP-核糖。NAADP信号转导尚未在哺乳动物中被证实 细胞，尽管合成和降解NAADP所需的酶 存在，初步数据表明，NAADP可能发生在 哺乳动物细胞。以下具体目标涉及以下问题 NAADP信号在哺乳动物细胞中是否起作用。1)NAADP是否 在哺乳动物细胞中发生？2)NAADP结合蛋白在 哺乳动物细胞？3)NAADP能诱导哺乳动物钙释放吗？ 系统？这些研究建议确定一种新的钙信号通路 在哺乳动物细胞中，这对我们理解 钙离子动员。

DESCRIPTION: (adapted from applicant's abstract) This application is in response to a program announcement for high-risk/high-impact research. The objective of the proposed research is to determine whether nicotinic adenine dinucleotide phosphate (NAADP) is a mediator of calcium mobilization in mammalian systems. NAADP is a metabolite of beta- nicotinamide adenine dinucleotide 2'-phosphate (beta-NADP) that has been found to mobilize calcium from intracellular stores in sea urchin eggs. This occurs by a mechanism distinct from those mediated by IP3 or cyclic ADP-ribose. NAADP signaling has not been demonstrated in mammalian cells, although the enzymes necessary to synthesize and degrade NAADP are present and preliminary data suggests that NAADP may occur in mammalian cells. The following specific aims address the question of whether NAADP signaling is operational in mammalian cells. 1) Does NAADP occur in mammalian cells? 2) Are NAADP binding proteins detectable in mammalian cells? 3) Can NAADP induce calcium release in mammalian systems? These studies propose to identify a new Ca signaling pathway in mammalian cells, with important implications for our understanding of calcium ion mobilization.