CELL ADHESION MOLECULES OF MAMMALIAN FERTILIZATION

该应用程序将研究哺乳动物精卵的分子事件 互动提供新的信息机制， 受精 一种哺乳动物精子蛋白， 将在老鼠身上进行研究。 长期目标是 了解受精事件的分子基础，从 精子膜蛋白异二聚体受精素，其a、B亚基 是一个蛋白质家族的成员，称为ADAM（A去整合素和A 金属蛋白酶结构域）或MDC（金属蛋白酶/去整合素/ 富含半胱氨酸）。 因为受精素中的去整合素结构域具有 与整联蛋白粘附分子的配体家族同源， 以前的研究提供了证据表明，受精素参与 精子-卵子相互作用，这项建议将研究这些作用 精卵粘附中受精素a和B的去整合素结构域， 小鼠模型 目的1将描述去整合素的作用 如果选择，通过测试受精中的受精素a和B的结构域 这些结构域中的氨基酸序列介导受精素A的结合， B结合于卵子，或抑制精子与卵子结合。 目标2将 通过使用重组体鉴定受精素a和B的结合配偶体， 这些精子蛋白的形式作为探针，以确定 小鼠卵、培养的细胞和噬菌体展示文库。 目标3 将研究受精素a和B在卵子中的可能作用， 通过确定重组形式的受精素A和/或 B诱导卵活化事件，例如，细胞内卵子数量增加 钙或多精受精块 从意义上说，该提案 指出，首先，这些研究的结果将是相关的 临床避孕的发展和了解形式 不育;第二，因为受精素a和B是最好的 特点ADAM/MDC成员，进一步我们的知识生育 将阐明可能的细胞粘附和信号转导作用， 这个家庭的其他成员。

This application will study molecular events of mammalian sperm-egg interaction to provide new information about the mechanism of fertilization. A mammalian sperm protein which is known to interact with the egg will be studied in mice. The long term objective is to understand the molecular basis of fertilization events, starting with the sperm membrane protein heterodimeric fertilin, whose a,b subunits are members of a protein family called, ADAM (A Disintegrin and A Metalloproteinase Domain) or MDC (Metalloproteinase/Disintegrin/ Cysteine-rich). Because the disintegrin domains in fertilin have homology to a family of ligands for integrin adhesion molecules and previous studies have provided evidence that fertilin is involved in sperm-egg interaction, this proposal will study the roles of these disintegrin domains of a and b fertilin in sperm-egg adhesion, in the mouse model. Aim 1 will characterize the roles of the disintegrin domains of fertilin a and b in fertilization by testing if selected amino acid sequences in these domains mediate binding of fertilin a and b to the egg, or inhibit the binding of sperm to eggs. Aim 2 will identify the binding partners of fertilin a and b by using recombinant forms of these sperm proteins as probes to identify binding partners on mouse eggs, on cultured cells, and in phage display libraries. Aim 3 will examine the possible involvement of fertilin a and b in egg activation by determining whether recombinant forms of fertilin a and/or b induce egg activation events, e.g., the rise in egg intracellular calcium or the polyspermy block. In terms of significance, the proposal states that, first, the results of these studies will be relevant clinically to contraceptive development and understanding forms of infertility; and, second, because fertilin a and b are the best characterized ADAM/MDC members, furthering our knowledge of fertilin will elucidate possible cell adhesion and signal transduction roles of other members in this family.