The Role of a Novel PIWI-Interacting Protein in Spermatogenesis

描述（申请人提供）：遗传物质从一代传给下一代，即从父母传给子女，是一个关键的生物学过程。然而，这一奋进是如何完成的，只是部分理解。我们以前发现一个称为Piwi蛋白的蛋白质家族对这一过程至关重要。为了更详细地了解Piwi的工作原理，我们鉴定了与Piwi相互作用的其他蛋白质。在果蝇中，Piwi与一种名为Papi的蛋白质相互作用;这种相互作用在进化上是保守的，因为小鼠和人类中的Piwi和Papi蛋白质也会相互作用。在果蝇中，Papi是胚胎正常发育和形成专门细胞（称为生殖细胞）所必需的，这些细胞将遗传信息传递给后代。然而，对于它如何在脊椎动物（如小鼠和人类）中发挥作用还一无所知。由于Papi是苍蝇胚胎的正确形成及其传递遗传信息的能力所必需的，并且由于其与Piwi蛋白的相互作用是高度保守的，因此我们假设这种相互作用对哺乳动物Papi蛋白的功能很重要。 在这里，我们提出的实验，将测试这一假设，并确定小鼠Papi（Mapi）在调节生殖系的作用。具体而言，我们建议1）检查Mapi在生殖系发育和成熟性腺中的表达模式，2）确定Mapi在出生后精子发生过程中的功能，3）表征Mapi蛋白和RNA复合物。 公共卫生相关性：有性繁殖的生物，如小鼠和人类，需要将其遗传信息从一代传递到下一代。这必须准确地完成，因为错误会导致后代出现严重的健康问题，并且需要体内高度专业化的组织来完成。该提案中的实验将定义一种蛋白质Mapi如何促进这一过程。

DESCRIPTION (provided by applicant): The passing of genetic material from one generation to the next, i.e. from parents to their children, is a key biological process. How this endeavor is accomplished, however, is only partially understood. We have previously found a family of proteins called the Piwi proteins to be essential for this process. To understand in more detail how Piwi works, we have identified additional proteins which interact with it. In flies, Piwi interacts with a protein called Papi; this interaction is evolutionarily conserved, as Piwi and Papi proteins in mouse and human also interact. In flies, Papi is required for proper development of the embryo and for formation of specialized cells (called germline) which pass genetic information to future generations. However, nothing is known about how it may function in vertebrates such as mice and humans. Because Papi is required for proper formation of fly embryos and their ability to transmit genetic information, and because its interaction with Piwi proteins are highly conserved, we hypothesize that this interaction is important for the function of mammalian Papi proteins. Here, we propose experiments which will test this hypothesis and determine the role of Mouse Papi (Mapi) in regulation of the germline. Specifically, we propose to 1) examine the expression patterns of Mapi during germline development and in mature gonads, 2) determine the function of Mapi during post-natal spermatogenesis, and 3) characterize Mapi protein and RNA complexes. PUBLIC HEALTH RELEVANCE: Sexually reproducing organisms, such as mice and humans, need to pass their genetic information from one generation to the next. This must be accomplished accurately, as mistakes can lead to severe health issues in the offspring, and requires highly specialized tissue in the body to do so. The experiments in this proposal will define how one protein, Mapi, contributes to this process.