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Lipid Signaling During Fertilization

受精过程中的脂质信号传导

基本信息

批准号：
0110609
负责人：
Bradley Stith
金额：
$ 33万
依托单位：
University of Colorado at Denver-Downtown Campus
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2001
资助国家：
美国
起止时间：
2001-08-01 至 2006-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=0110609&HistoricalAwards=false
关键词：
Lipid Signaling During Fertilization

项目摘要

0110609StithAlthough the major event of fertilization is known to be the release of intracellular calcium, the exact cause of this calcium release is unknown. Activation of phospholipase C appears to be required for the release of calcium at fertilization; however, it is not known how this enzyme is activated. One possible path to activation of phospholipase C may be through another lipid signaling path. In an effort to quantify various lipid signaling paths, it has been noted that the mass of sphingomyelin, phosphatidylcholine and phosphatidylinositol decrease whereas choline, IP3, DAG and phosphatidic acid increase (phosphatidylethanolamine and phosphatidylserine do not change) during Xenopus fertilization. From these data and others, it is suggested that phospholipase D plays an important role in fertilization. Phosphatidic acid is a product of the reaction catalyzed by phospholipase D. Phosphatidic acid may be required for membrane fusion events (e.g.: sperm-egg merger, cortical granule-plasma membrane merger) and the DAG increase (since phosphatidic acid can be dephosphorylated to DAG) at fertilization. Most importantly, phosphatidic acid binds to and activates phospholipase C; thus, phosphatidic acid from sperm or that produced in the newly formed zygote may induce the central event of fertilization: the increase in intracellular calcium. Through the use of exogenous phosphatidic acid, or inhibition of phospholipase D, the role of this enzyme and the product phosphatidic acid in fertilization will be examined.

尽管受精的主要过程是细胞内钙的释放，但这种钙释放的确切原因尚不清楚。磷脂酶C的激活似乎是受精时钙释放所必需的;然而，尚不清楚这种酶是如何激活的。磷脂酶C激活的一个可能途径可能是通过另一个脂质信号通路。在努力量化各种脂质信号通路中，已经注意到，在爪蟾受精过程中，鞘磷脂、磷脂酰胆碱和磷脂酰肌醇的质量减少，而胆碱、IP 3、DAG和磷脂酸增加（磷脂酰乙醇胺和磷脂酰丝氨酸不改变）。从这些数据和其他人，磷脂酶D在受精中起着重要的作用。磷脂酸是磷脂酶D催化的反应产物。膜融合事件可能需要磷脂酸（例如：精子-卵子合并，皮质颗粒-质膜合并）和DAG增加（因为磷脂酸可以去磷酸化为DAG）。最重要的是，磷脂酸结合并激活磷脂酶C;因此，来自精子或新形成的受精卵中产生的磷脂酸可能诱导受精的中心事件：细胞内钙的增加。通过使用外源磷脂酸或抑制磷脂酶D，将检查这种酶及其产物磷脂酸在受精中的作用。