Regulation of meiotic arrest by a Gs-linked receptor

Gs 连锁受体对减数分裂停滞的调节

• 批准号: 6941436
• 负责人: LAURINDA A. JAFFE
• 金额: $ 26.37万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-15 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6941436
• 关键词: biological signal transduction; cell cell interaction; cell growth regulation; cell surface receptors; gene targeting; genetically modified animals; granulosa cell; human tissue; laboratory mouse; luteinizing hormone; meiosis; oogenesis; phenotype

DESCRIPTION (provided by applicant): The mammalian ovarian follicle presents a remarkable example of how cells communicate to regulate the cell cycle within a complex tissue. In particular, the somatic cells that surround the oocyte send a signal to the oocyte that maintains meiotic prophase arrest, and then in response to luteinizing hormone (LH), these same somatic cells send an opposite signal, causing meiosis to resume. Recent work from this laboratory has shown that the maintenance of prophase arrest requires the activity of a heterotrimeric G protein of the Gs family, and a Gs-linked receptor, GPR3, both located in the oocyte. The proposed studies will investigate the function of GPR3 in maintaining prophase arrest, as well as in restarting the meiotic cell cycle. Aim one is to examine the expression of Gpr3 during oogenesis, to further characterize the phenotype of a Gpr3 knockout mouse, and to determine whether the Gpr3 requirement for the maintenance of meiotic arrest is due entirely to GPR3 in the oocyte. Aim two is to investigate whether and how the presence of the somatic cells maintains the activities of Gs and GPR3 in follicle-enclosed oocytes at levels greater than those in isolated oocytes. Aim three is to investigate whether and how signals from the somatic cells decrease the activities of Gs and GPR3 during LH-induced reinitiation of meiosis. These studies will provide important new insights into the function of G-protein linked receptors in cell-cell signaling and cell cycle regulation. Ultimately, this knowledge concerning the regulation of the normal cell cycle may be applicable to treatment of pathological conditions in which cell cycle control is lost.

描述（由申请人提供）：哺乳动物卵巢卵泡提供了一个非凡的例子，说明了细胞如何在复杂组织中进行调节细胞周期。特别是，围绕卵母细胞的体细胞向卵母细胞发出信号，该卵母细胞保持减数分裂预言，然后为了响应黄体生成激素（LH），这些相同的体细胞发出了相反的信号，导致减数分裂恢复。该实验室的最新工作表明，预言骤停的维持需要GS家族的异三聚体G蛋白的活性，而GS连接的受体GPR3都位于卵母细胞中。 拟议的研究将研究GPR3在维持预言停滞以及重新启动减数分裂细胞周期方面的功能。目的是检查卵子发生过程中GPR3的表达，以进一步表征GPR3敲除小鼠的表型，并确定GPR3维持减数分裂停滞的要求是否完全归因于卵母细胞中的GPR3。目标二是研究体细胞的存在以及如何在卵泡封闭的卵母细胞中的GS和GPR3的活性以比分离的卵母细胞中的水平更高。目的三是调查来自体细胞的信号以及如何在LH诱导的减数分裂重新定量期间降低GS和GPR3的活性。这些研究将为G蛋白连接受体在细胞 - 细胞信号传导和细胞周期调节中的功能提供重要的新见解。 最终，有关正常细胞周期调节的这种知识可能适用于丢失细胞周期控制的病理条件的治疗。