NAADP SIGNALING IN MAMMALIAN SYSTEMS

哺乳动物系统中的 NAADP 信号传导

• 批准号: 6151224
• 负责人: TIMOTHY Francis WALSETH
• 金额: $ 10.29万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6151224
• 关键词: Mammalia; NAD(H) phosphate; affinity labeling; binding proteins; biological signal transduction; calcium flux; cell line; membrane permeability; microsomes; radiotracer; sea urchins

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.

描述：（改编自申请人的摘要）本申请在 对高风险/高影响研究计划公告的回应。 这项研究的目的是确定尼古丁是否 腺嘌呤二核苷酸磷酸（NAADP）是钙离子的介质 在哺乳动物系统中的动员。NAADP是β- 烟酰胺腺嘌呤二核苷酸2 '-磷酸（beta-NADP）， 发现从海胆卵的细胞内储存中动员钙。 这是通过与IP 3或环状磷酸化介导的机制不同的机制发生的。 ADP-核糖。NAADP信号转导尚未在哺乳动物中得到证实。 细胞，虽然合成和降解NAADP所必需的酶 目前，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信号传导是否在哺乳动物细胞中起作用。1)NAADP是否 发生在哺乳动物细胞中2)NAADP结合蛋白是否可在 哺乳动物细胞3)NAADP能诱导哺乳动物钙释放吗 系统？这些研究提出了一种新的钙信号通路 在哺乳动物细胞中，这对我们理解 钙离子的流动。