Department of Biomedical Sciences, T4-018 Veterinary Research Tower, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Brain Res. 2010 Dec 10;1364:53-61. doi: 10.1016/j.brainres.2010.09.008. Epub 2010 Sep 15.
The binding of hypothalamic gonadotropin-releasing hormone (GnRH) to the pituitary GnRH receptor (GnRHR) is essential for reproductive function by stimulating the synthesis and secretion of gonadotropic hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH). Engagement of the GnRHR by GnRH initiates a complex series of signaling events that include the activation of various mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK). GnRHR signaling is thought to initiate within specialized microdomains in the plasma membrane termed membrane rafts. These microdomains are enriched in sphingolipid and cholesterol and are believed to be highly dynamic organizing centers for receptors and their cognate signaling molecules associated with the plasma membrane. Within this review we discuss the composition and role of membrane rafts in cell signaling and examine evidence that the mammalian type I GnRHR is constitutively and exclusively localized to these membrane microdomains in various experimental models. We conclude that membrane raft composition and organization potentially underlie the functional ability of GnRH to elicit the assembly of multi-protein signaling complexes necessary for downstream signaling to the ERK pathway that ultimately is critical for controlling fertility.
下丘脑促性腺激素释放激素（GnRH）与垂体 GnRH 受体（GnRHR）的结合对于生殖功能至关重要，它可以刺激促性腺激素、黄体生成素（LH）和卵泡刺激素（FSH）的合成和分泌。GnRH 与 GnRHR 的结合启动了一系列复杂的信号事件，包括各种丝裂原活化蛋白激酶（MAPK）途径的激活，包括细胞外信号调节激酶（ERK）。GnRHR 信号被认为是在质膜中称为膜筏的特殊微域内起始的。这些微域富含鞘脂和胆固醇，被认为是与质膜相关的受体及其同源信号分子的高度动态组织中心。在这篇综述中，我们讨论了膜筏在细胞信号转导中的组成和作用，并研究了证据表明，哺乳动物 I 型 GnRHR 在各种实验模型中都被组成性地和专一地定位于这些膜微域中。我们得出结论，膜筏的组成和组织可能是 GnRH 发挥功能的基础，它能够募集多蛋白信号复合物，这些复合物对于下游 ERK 途径的信号转导至关重要，最终对于控制生育能力至关重要。
