Identification of an oocyte maturation hormone receptor

卵母细胞成熟激素受体的鉴定

• 批准号: 6761899
• 负责人: KATHLEEN R FOLTZ
• 金额: $ 7.38万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6761899
• 关键词: Asteroidea; G protein; Xenopus; Xenopus oocyte; biological signal transduction; cell growth regulation; chickens; complementary DNA; egg /ovum; hormone receptor; polymerase chain reaction

DESCRIPTION (provided by applicant): In nearly all animals, fully-grown oocytes remain arrested in meiosis for some time until hormones break this arrest by activating poorly understood, complex signal transduction pathways that culminate in the resumption of the cell cycle. This crucial step confers the capacity of the oocyte to respond to sperm. This process of converting the arrested oocyte into a fertilization competent egg is termed maturation. While oocyte maturation is a widely conserved process across all animal species, and some information is known about the hormones that regulate maturation, no oocyte maturation hormone receptor has been identified unambiguously in any species to date, defining a major gap in our understanding of this fundamental event. This proposal outlines a novel strategy designed to identify an oocyte maturation hormone receptor in a simple model system, the starfish oocyte. The starfish was chosen as the model system because the maturation-inducing hormone 1-methyladenine (1-MA) has been identified, and knowledge that the signaling pathway is G-protein linked provides information that will be used to identify the receptor. Distinct homology-based and functional cloning approaches will be used in a tandem effort to identify the cDNA encoding the 1-MA receptor. Identification and characterization of the 1-MA receptor will allow us to then test the widely-held hypothesis that this receptor is a canonical G-protein coupled receptor (GPCR) and eventually, to assess the signaling pathway leading from hormone at the oocyte surface to resumption of meiosis. Further, success using this strategy would provide proof of concept for investigations of the maturation hormone receptors of other species, including mammals. Further, beyond the obvious reproductive biology aspects of the project, oocytes are a good model system in which to understand basic cell signaling events. Finally, cancers result from an abnormal and unregulated growth of cells, which often is normally regulated by signaling cascades involving GPCRs. Therefore, the oocyte maturation studies proposed here potentially will provide new insights for the mechanisms of cell growth regulation and perhaps lead to a deeper understanding of how cancer develops.

描述（由申请人提供）：在几乎所有动物中，完全生长的卵母细胞在减数分裂中仍然被捕一段时间，直到激活良好理解的，不理解的，复杂的信号转导途径，这些途径在细胞周期的恢复中达到最终形式。这个关键步骤赋予了卵母细胞对精子反应的能力。将被捕的卵母细胞转化为受精蛋的这种过程称为成熟。虽然卵母细胞成熟是所有动物物种中广泛保守的过程，并且有关调节成熟的激素的某些信息，但迄今为止，在任何物种中都没有明确地确定卵母细胞成熟激素受体，这在我们对这一基本事件的理解中定义了一个主要差距。该建议概述了一种新型策略，旨在识别简单模型系统中的卵母细胞成熟激素受体，即海星卵母细胞。之所以选择海星作为模型系统，是因为已经鉴定出成熟的激素1-甲基丹宁（1-MA），并且知道信号传导途径是G蛋白链接的，提供了将用于识别受体的信息。基于同源性和功能性克隆方法的不同努力将用于识别编码1-MA受体的cDNA。 1-MA受体的鉴定和表征将使我们能够检验广泛控制的假说，即该受体是一种规范的G蛋白偶联受体（GPCR），并最终评估从卵母细胞表面上的激素引起的荷尔蒙引起的信号传导途径。此外，使用该策略的成功将为研究其他物种（包括哺乳动物）的成熟激素受体提供概念证明。此外，除了项目明显的生殖生物学方面，卵母细胞是一个很好的模型系统，可以在其中了解基本的细胞信号事件。最后，癌症是由细胞的异常和不调节的生长引起的，通常通常通过涉及GPCR的信号级联反应来调节。因此，此处提出的卵母细胞成熟研究可能会为细胞生长调节机制提供新的见解，并可能导致对癌症的发展方式有更深入的了解。