Regulation of meiotic arrest by a Gs-linked receptor

描述（由申请人提供）：哺乳动物卵泡是细胞如何交流以调节复杂组织内细胞周期的一个显著例子。特别是，卵母细胞周围的体细胞向卵母细胞发送维持减数分裂前期停滞的信号，然后响应于促黄体生成激素（LH），这些相同的体细胞发送相反的信号，导致减数分裂恢复。该实验室最近的工作表明，维持前期停滞需要Gs家族的异源三聚体G蛋白和Gs相关受体GPR3的活性，两者都位于卵母细胞中。 该研究将探讨GPR3在维持前期停滞以及重新启动减数分裂细胞周期中的功能。目的之一是检查GPR3在卵子发生过程中的表达，以进一步表征GPR3敲除小鼠的表型，并确定是否GPR3维持减数分裂停滞的要求是完全由于GPR3在卵母细胞。目的二是研究体细胞的存在是否以及如何维持卵泡封闭卵母细胞中Gs和GPR3的活性高于分离卵母细胞中的活性。目的三是研究在LH诱导的减数分裂重新启动过程中体细胞信号是否以及如何降低Gs和GPR3的活性。这些研究将为G蛋白连接受体在细胞间信号传导和细胞周期调控中的功能提供重要的新见解。 最终，这种关于正常细胞周期调节的知识可适用于治疗细胞周期控制丧失的病理状况。

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.