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都会停滞一段时间，直到激素通过激活人们知之甚少的复杂信号转导途径来打破这种停滞，最终导致细胞周期的恢复。这一关键步骤赋予卵母细胞对精子做出反应的能力。将停滞的卵母细胞转化为具有受精能力的卵子的过程称为成熟。虽然卵母细胞成熟是所有动物物种中广泛保守的过程，并且已知一些有关调节成熟的激素的信息，但迄今为止，在任何物种中尚未明确鉴定出卵母细胞成熟激素受体，这在我们对这一基本原理的理解上存在重大差距事件。该提案概述了一种新策略，旨在识别简单模型系统（海星卵母细胞）中的卵母细胞成熟激素受体。选择海星作为模型系统是因为成熟诱导激素 1-甲基腺嘌呤 (1-MA) 已被识别，并且信号通路与 G 蛋白相关的知识提供了可用于识别受体的信息。将使用不同的基于同源性的克隆方法和功能性克隆方法来共同鉴定编码 1-MA 受体的 cDNA。 1-MA 受体的鉴定和表征将使我们能够测试广泛持有的假设，即该受体是典型的 G 蛋白偶联受体 (GPCR)，并最终评估从卵母细胞表面的激素到减数分裂的恢复。此外，使用这种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，除了该项目明显的生殖生物学方面之外，卵母细胞是了解基本细胞信号传导事件的良好模型系统。最后，癌症是由细胞异常且不受调节的生长引起的，细胞生长通常受到涉及 GPCR 的信号级联反应的调节。因此，这里提出的卵母细胞成熟研究可能将为细胞生长调节机制提供新的见解，并可能导致对癌症如何发展的更深入的了解。