REGULATION OF CA SIGNALING DURING OOGENESIS

钙信号是通过胞浆钙的升高来调节的， 要么是通过细胞内钙释放，要么是通过细胞内钙内流 细胞外空间。在不可兴奋的细胞中，主要的钙进入途径 是商店操作的钙质入口。钙是一种普遍存在的第二信使 对许多细胞反应都很重要，包括基因转录， 受精、收缩、分泌、细胞增殖和凋亡。 钙如何调节这些不同的细胞反应，通常是在相同的 细胞，是不清楚的。此外，钙信号在细胞周期中的调节作用 细胞周期没有很好的定义。这项提案涉及监管和 非洲爪哇卵母细胞减数分裂过程中钙信号的特异性。非洲爪哇卵母细胞 为这些研究提供了一个很好的模型，因为在卵母细胞成熟过程中， 两条主要的钙信号通路，即IP3依赖的钙释放 和SOCE，经历了戏剧性的变化。依赖IP3的钙释放增强 几个折叠和SOCE在减数分裂过程中以某种方式失活。确定如何 这些钙信号通路在减数分裂过程中被调节将改善我们的 了解钙信号调节。非洲爪哇的另一个优势 卵母细胞含有钙激活的氯电流，这种电流可以 用作不同钙信号如何影响下游的实时指示器 效应器，从而提高我们对钙信号特异性的理解。这个 该提案的具体目标是：1)描述空间和时间 IP3介导的钙释放和SOCE在整个卵子发生过程中的特征 阐明SOCE失活和增强的调控机制 IP3介导的减数分裂释放；3)在小鼠卵母细胞中记录SOCE，以及 测试它在减数分裂过程中是否失活。在非洲爪哇的卵母细胞研究中， 钙激活的氯电流将作为下游效应器进行测量 钙信号。钙信号对细胞增殖和 与癌症的发展有牵连。此外，SOCE被下调了监管 在来自原发免疫缺陷患者的T细胞中，暗示它是一种 免疫反应中的基本信号通路。因此，除了 这项工作有助于更好地了解钙信号转导 将提供对钙信号在疾病中的作用的见解，例如 癌症和免疫缺陷。

Calcium signaling is mediated by a rise in cytoplasmic calcium, either by calcium release from intracellular stores or calcium influx from the extracellular space. In non-excitable cells, the primary calcium entry pathway is Store Operated Calcium Entry. Calcium is a ubiquitous second messenger that is important for many cellular responses, including gene transcription, fertilization, contraction, secretion, cellular proliferation, and apoptosis. How calcium mediates these different cellular responses, often in the same cell, is not clear. Furthermore, the modulation of calcium signaling during the cell cycle is not well defined. This proposal addresses the regulation and specificity of calcium signaling during Xenopus oocyte meiosis. Xenopus oocytes provide a good model for these studies because during oocyte maturation, the two primary calcium signaling pathways, namely IP3 dependent calcium release and SOCE, undergo dramatic changes. IP3-dependent calcium release is enhanced several fold and SOCE is somehow inactivated during meiosis. Determining how these calcium signaling pathways are regulated during meiosis will improve our understanding of calcium signal regulation. An additional advantage of Xenopus oocytes is that they contain calcium-activated chloride currents that can be used as real time indicators of how different calcium signals affect downstream effectors, thus improving our understanding of calcium signal specificity. The specific aims of the proposal are: 1) characterize the spatial and temporal features of IP3-mediated calcium release and SOCE throughout oogenesis; 2) elucidate the mechanisms regulating SOCE inactivation, and increased IP3-mediated release during meiosis; and 3) record SOCE in mouse oocytes, and test whether it is inactivated during meiosis. In the Xenopus oocyte studies, calcium-activated Cl currents will be measured as downstream effectors of calcium signals. Calcium signaling is important for cellular proliferation and has been implicated in cancer development. Furthermore, SOCE is downregulated in T-cells from patients with primary immunodeficiency, implicating it as an essential signaling pathway in the immune response. Therefore, in addition to contributing to a better basic understanding of calcium signaling, this work will offer insights into the role of calcium signaling in diseases, such as cancer and immunodeficiency.