ACROSOMAL ENZYME BIOSYNTHESIS BY SPERMATIDS

人们坚定地认为精子顶体对于 受精。精子顶体形成不良的男性或 完全缺乏顶体是不育的。广泛的、长期的 这项研究计划的目的是了解 通过研究靶向、分离和作用形成顶体 顶体生物发生过程中顶体蛋白的变化。根据最近的情况 在细胞内蛋白质靶向领域的进展，是最多的 认为精子顶体是一种受调节的分泌物是合适的 颗粒剂。目前的模型认为，将蛋白质分离成 受调节的分泌颗粒通过选择性聚集发生 形成颗粒复合体，形成致密的 这些基因。精子顶体包括作为其致密部分的 核心是由单体组成的两个高分子量蛋白质 多肽由50,000个MR(AM50)和67,000个MR(AM67)组成。AM50 是五角蛋白家族的新成员，AM67是一种 补体结合蛋白超家族的新成员。在……里面 根据它们的相对丰度，可能的配体结合性质， 和本提案中提出的其他考虑因素，工作 假说认为，AM50和AM67是 正在发育的顶体的靶向/组装装置。至 研究顶体生物发生，提出了五个具体目标。这个 首先是检查发育中的顶体内的定位。 几种主要的顶体蛋白，并确定这些 蛋白质相互结合形成顶体的致密核心 被称为顶体基质。第二个目标是确定 AM50是否具有与血清类似的配体结合特性 五氯氰菊酯。第三个目标是确定Am67是否有 性质类似于补体结合蛋白。第四个目标是 以确定Am67是否与小鼠ssp56密切相关 被认为是精子表面结合蛋白的蛋白质 卵子的透明带是同源蛋白。第五个目标是 检查各种调节分子以确定它们是否 影响顶体成分的合成和组装。 在审查这些问题时，该项目将使用多学科 涉及形态学、细胞生物学和生物化学的方法。 这些实验将提供有关该角色的新信息 这些新的蛋白质在顶体生物发生和生殖中的作用。 这些研究的结果可以应用于诊断 某些男性不育的病例。

It is firmly established that the sperm acrosome is essential for fertilization. Males whose sperm have poorly formed acrosomes or lack acrosomes altogether are infertile. The broad, long-term objective of this research proposal is to understand the process of acrosome formation by examining the targeting, segregation, and role of acrosomal proteins during acrosome biogenesis. In light of recent advances in the field of protein targeting within the cell, is it most appropriate to consider the sperm acrosome as a regulated secretory granule. Current models propose that the segregation of proteins into regulated secretory granules occurs through the selective aggregation of proteins into a particulate complex that become the dense core of these genules. The sperm acrosome includes as part of its dense core, two high molecular weight proteins comprised of the monomer ploypeptides of 50,000 Mr (AM50) and 67,000 Mr (AM67). AM50 is a novel member of the pentraxin family of proteins and AM67 is a novel member of the complement-binding protein superfamily. In light of their relative abundance, probable ligand-binding properties, and other considerations presented in this proposal, the working hypothesis is that AM50 and AM67 are essential parts of the targeting/assembly apparatus of the developing acrosome. To examine acrosome biogenesis, five specific aims are proposed. The first is to examine the localization within the developing acrosome of several major acrosomal proteins and to determine whether these proteins bind with each other to form the dense core of the acrosome called the acrosomal matrix. The second aim is to determine whether AM50 has ligand-binding properties similar to serum pentraxins. The third aims is to determine whether Am67 has properties similar to complement-binding proteins. The fourth aim is to determine whether Am67 and mouse ssp56, a closely related protein proposed to be the sperm surface binding protein for the egg's zona pellucida, are orthologous proteins. The fifth aim is to examine various regulatory molecules to determine whether they influence the synthesis and assembly of the acrosomal components. The examine these questions, the project will use a multidisciplinary approach involving morphology, cell biology, and biochemistry. These experiments will provide new information concerning the role of these novel proteins in acrosome biogenesis and reproduction. Results from these studies could find application in the diagnosis of certain cases of male infertility.