Mammalian Gamete Surface Organization and Function

哺乳动物配子表面组织和功能

• 批准号: 6871332
• 负责人: Diana G Myles
• 金额: $ 33.19万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6871332
• 关键词: acrosome; cell adhesion; cell adhesion molecules; cell cell interaction; egg /ovum; enzyme activity; enzyme substrate; fertilization; gene targeting; genetically modified animals; laboratory mouse; lipids; membrane fusion; membrane proteins; metalloendopeptidases; protein binding; protein localization; protein structure function; sperm; surface property; tissue /cell culture

DESCRIPTION (provided by applicant): Sperm-egg fusion occurs at a critical moment in fertilization at which the zygote is formed. In recent progress key proteins on the gamete surfaces have been implicated in membrane fusion. Current evidence indicates: (1) sperm ADAMs may have a role in fusion and (2) the egg tetraspanin CD9 and egg GPI-anchored proteins are required for fusion. ADAM proteins potentially have either cell-cell adhesion activity or protease activity and we propose that each of these is required for normal fertilization. Although gene knockout studies have shown that ADAMs 1, 2 and 3 are not required for fusion, it is possible that other ADAM family members have a role. We will test if a different ADAM acts in fusion of the sperm and egg plasma membranes. We will also test if a known protease, ADAM 24, acts to create the membrane block to polyspermy. Since gene deletion studies have shown that egg CD9 is required for fusion, we focus on CD9's mechanism of action and its localization to lipid microdomains. CD9 is known to have a soluble ligand and we will test if sperm have a related transmembrane ligand to which CD9 binds. In tissue culture lines, CD9 associates with many other proteins on the surface of a CD9-expressing cell. We will test if an egg CD9-associated protein binds to the sperm surface. Gene knockout studies have also shown that egg GPI-anchored proteins are required for fusion. We propose to identify the critical GPl-anchored protein(s) and analyze its mode of action. Since multiple proteins appear to play a role in fusion, we ask how their activities are coordinated. We propose that to function in fusion the active egg molecules must be organized into lipid microdomains. Thus, these studies are designed to combine molecular and cellular levels to bring new insight into the process of gamete membrane fusion.

描述（由申请人提供）：精卵融合发生在受精过程中受精卵形成的关键时刻。在最近的进展中，配子表面的关键蛋白参与了膜融合。目前的证据表明：(1)精子的ADAMs可能在融合中起作用；(2)卵子的tetraspanin CD9和卵子gpi锚定蛋白是融合所必需的。