A Signaling Pathway that Couples Spore Formation to the Completion of Meiosis in S. Cerevisiae.

智力价值：减数分裂是从二倍体产生单倍体的细胞分裂程序。减数分裂的完成与产生配子的分化程序相结合。本项目将使用酿酒酵母中的产孢子，作为一个模型系统来研究配子形成与完成减数分裂的信号通路。Smk1是一种减数分裂特异的MAPK，它控制着孢子形成的减数分裂后程序。Smk1被磷酸化激活，减数分裂由CDK激活的激酶Cak1完成。后期促进复合体(APC)泛素连接酶的减数分裂特异性靶向亚基AMA1调节Cak1/Smk1反应。此外，Smk1的激活还需要Ssp2，一种生化功能未知的减数分裂特异蛋白。总之，这些发现表明，依赖于AMA1的一种未知抑制蛋白的蛋白分解和Ssp2的关联，控制了Cak1对Smk1的激活。这个项目的一个目标是确定Cak1和Ssp2如何激活Smk1。第二个目的是确定AMA1靶向破坏的Smk1抑制物，并阐明该抑制物如何控制Smk1的激活。这个项目中研究的大多数蛋白质在进化上是保守的。因此，这项研究很可能会产生可检验的假说，说明减数分裂和配子形成在其他生物体中是如何耦合的。因此，这些研究将加快在包括其他微生物、植物和动物在内的广泛生物中研究配子发生的步伐。更广泛的影响：该项目提供了一个绝佳的机会，培训博士前学生进行假设驱动的研究。为了增加对本科生的影响，首席研究员将与罗斯蒙特学院的一名教育工作者合作，后者对研究酵母的减数分裂调控感兴趣，并让有才华的本科生参与科学发现的过程。这种伙伴关系通过促进教育工作者、研究人员、博士前实习生和本科生之间的互动，将教育目标与本实验室的研究活动相结合。

Intellectual Merit:Meiosis is the cell division program that produces haploids from diploids. The completion of meiosis is coupled to differentiation programs that generate gametes. This project will use sporulation in the yeast Saccharomyces cerevisiae, as a model system to study signaling pathways that couple gamete formation to the completion of meiosis. Smk1 is a meiosis-specific MAPK that controls the post-meiotic program of spore formation. Smk1 is activated by phosphorylation as meiosis is being completed by the CDK activating kinase, Cak1. A meiosis-specific targeting-subunit of the anaphase promoting complex (APC) ubiquitin-ligase named Ama1 regulates the Cak1/Smk1 reaction. In addition, Ssp2, a meiosis-specific protein of unknown biochemical function is required for Smk1 activation. Collectively, these findings indicate that Ama1-dependent proteolysis of an unidentified inhibitor protein, and the association of Ssp2, control the activation of Smk1 by Cak1. One aim of this project is to establish how Cak1 and Ssp2 activate Smk1. A second aim is to identify the inhibitor of Smk1 that is targeted for destruction by Ama1 and elucidate how this inhibitor controls Smk1 activation. Most of the proteins studied in this project are evolutionarily conserved. It is therefore likely that the research will generate testable hypotheses for how meiosis and gamete formation are coupled in other organisms. As such, these studies will accelerate the pace of research on gametogenesis in a broad range of organisms including other microorganisms, plants, and animals. Broader impact: The project provides an outstanding opportunity to train pre-doctoral students in hypothesis-driven research. To increase the impact at the undergraduate level, the principal investigator will partner with an educator at Rosemont College who is interested in studying meiotic regulation in yeast and involving talented undergraduates in the process of scientific discovery. This partnership integrates educational objectives with the research activities of this laboratory by promoting interaction between educators, researchers, predoctoral trainees, and undergraduate students.