ACROSOMAL ENZYME BIOSYNTHESIS BY SPERMATIDS

精子顶体酶的生物合成

• 批准号: 2673549
• 负责人: George L. Gerton
• 金额: $ 21.46万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673549
• 关键词: acrosin; acrosome; binding proteins; enzyme biosynthesis; fertility; guinea pigs; immunocytochemistry; in situ hybridization; intracellular transport; laboratory mouse; posttranslational modifications; protein biosynthesis; protein structure function; sperm; spermatogenesis; tissue /cell culture; transfection

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.

精子顶体对于精子的发育是必不可少的， 受精 精子顶体形成不良的男性，或 缺乏顶体的不育。 广泛、长期 本研究的目的是了解 通过检查靶向、分离和作用， 顶体生物发生过程中顶体蛋白的变化。 鉴于最近 在细胞内蛋白质靶向领域的进展，是最 适当考虑精子顶体作为一个调节分泌 颗粒。 目前的模型提出，蛋白质分离成 调节分泌颗粒通过选择性聚集发生 形成一个颗粒状的复合体， 这些基因。 精子顶体包括致密的 核心，由单体组成的两种高分子量蛋白质 50，000 Mr（AM 50）和67，000 Mr（AM 67）的多肽。 AM50 AM 67是五聚蛋白家族的新成员，AM 67是五聚蛋白家族的新成员。 补体结合蛋白超家族的新成员。 在 根据它们的相对丰度，可能的配体结合特性， 以及本提案中提出的其他考虑因素， 假设AM 50和AM 67是 发育中的顶体的靶向/组装装置。到 研究顶体生物发生，提出了五个具体目标。 的 首先是检查发育中的顶体内的定位， 几种主要的顶体蛋白，并确定这些蛋白是否 蛋白质相互结合形成顶体的致密核心 称为顶体基质。 第二个目标是确定 AM 50是否具有与血清相似的配体结合特性 正五聚素第三个目标是确定Am 67是否具有 性质类似于补体结合蛋白。 第四个目标是 为了确定Am 67和小鼠ssp 56是否密切相关， 蛋白质被认为是精子表面结合蛋白， 卵的透明质酸是直链淀粉蛋白。第五个目标是 检查各种调节分子，以确定它们是否 影响顶体组分的合成和组装。 在研究这些问题时，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。 这些实验将提供关于 这些新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 某些男性不育症