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）此申请在 对高风险/高影响力研究的计划公告的响应。 拟议研究的目的是确定烟碱是否是否 腺嘌呤二核苷酸磷酸盐（NAADP）是钙的介体 哺乳动物系统中的动员。 NAADP是β-的代谢物 烟酰胺腺嘌呤二核苷酸2'-磷酸（β-NADP） 发现从海胆卵中的细胞内存储中动员钙。 这是通过与IP3或循环介导的机制不同的机制 ADP-ribose。 NAADP信号在哺乳动物中尚未证明 细胞，尽管合成和降解NAADP所需的酶 存在并初步数据表明NAADP可能发生在 哺乳动物细胞。以下具体目的解决了 NAADP信号是否在哺乳动物细胞中运行。 1）做NAADP 发生在哺乳动物细胞中？ 2）是可检测到的NAADP结合蛋白 哺乳动物细胞？ 3）NAADP可以在哺乳动物中诱导钙释放 系统？这些研究建议识别新的CA信号通路 在哺乳动物细胞中，对我们的理解具有重要意义 钙离子动员。