Cell Signaling in Meiosis

减数分裂中的细胞信号转导

• 批准号: 6771014
• 负责人: JOANNE ENGEBRECHT
• 金额: $ 27.47万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6771014
• 关键词: Saccharomyces cerevisiae; biological signal transduction; cell differentiation; cytogenetics; developmental genetics; electron microscopy; fungal genetics; green fluorescent proteins; meiosis; membrane activity; membrane permeability; phospholipase D; protein kinase; protein structure function; sporogenesis

DESCRIPTION (provided by applicant): Gametogenesis is essential for the propagation of all sexually reproducing organisms and consists of halving the chromosome number through meiosis, and the subsequent packaging of the haploid products into gametes (sperm and eggs in mammals). Meiosis and gamete formation must be tightly coupled to ensure the formation of viable progeny; perturbations result in infertility, inviability and birth defects. Not surprisingly, a large number of signaling molecules participate in precisely regulating this cellular differentiation program. In the yeast Saccharomyces cerevisiae, sexual reproduction occurs via sporulation and is similar in many respects to gametogenesis in mammals. We have shown that the conserved signaling molecules Phospholipase D (PLO) and the Ste2O-like kinase, Sps1 are essential for yeast sporulation, but their precise roles in this process are largely unknown.We propose to continue to exploit the genetics of yeast to elucidate the signaling pathways involved in regulating the cellular differentiation program of sporulation. We will analyze the role of PLO and Sps1 using a three-pronged approach: 1) we wilt investigate the specific requirement for PLO-generated lipids in sporulation. 2) We will elucidate the function of a developmentally regulated Art-GAP and determine if it mediates PLO pathway function. 3) We will examine the relationship between PLD and Sps1 and identify additional components of the Sps1 signaling pathway. Taken together, our studies will provide a framework for understanding how cell signaling events are coordinated to ensure the formation of viable progeny. Given the extensive degree of evolutionary conservation between these molecules, it is likely that an understanding of the function of PLD and Sps1 in yeast wilt provide general insights into the role of orthologous molecules in humans and the consequences of their altered regulation in infertility, birth defects and disease.

描述（由申请人提供）：配子发生对所有有性繁殖的生物体的繁殖至关重要，包括通过减数分裂使染色体数量减半，随后将单倍体产品包装成配子（哺乳动物的精子和卵子）。减数分裂和配子形成必须紧密耦合，以确保形成可存活的后代；扰动导致不孕、不能生存和出生缺陷。毫不奇怪，大量的信号分子参与了细胞分化过程的精确调节。在酿酒酵母中，有性生殖是通过产孢进行的，在许多方面与哺乳动物的配子发生相似。我们已经证明，保守的信号分子磷脂酶D （PLO）和ste20样激酶Sps1对酵母产孢至关重要，但它们在这一过程中的确切作用在很大程度上是未知的。我们建议继续利用酵母的遗传学来阐明调控孢子形成的细胞分化程序的信号通路。我们将采用三管齐下的方法分析PLO和Sps1的作用：1)我们将研究孢子形成过程中对PLO生成的脂质的特定需求。2)我们将阐明发育调控的Art-GAP的功能，并确定它是否介导PLO通路功能。3)我们将研究PLD和Sps1之间的关系，并确定Sps1信号通路的其他成分。综上所述，我们的研究将为理解细胞信号事件如何协调以确保可存活后代的形成提供一个框架。考虑到这些分子之间广泛的进化保守性，对PLD和Sps1在酵母中的功能的理解可能会为人类中同源分子的作用以及它们在不育、出生缺陷和疾病中的调节改变的后果提供一般的见解。