REGULATION OF CA SIGNALING DURING OOGENESIS

钙信号传导是由细胞质钙的升高介导的， 通过从细胞内储存的钙释放或从细胞内的钙流入， 细胞外间隙在非兴奋性细胞中，主要的钙离子进入途径 是钙库操作的钙进入。钙是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。 钙如何介导这些不同的细胞反应，通常在相同的 细胞，并不清楚。此外，钙信号的调节过程中， 细胞周期并不明确。该提案涉及法规和 非洲爪蟾卵母细胞减数分裂过程中钙信号的特异性。爪蟾卵母细胞 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， 两种主要的钙信号通路，即IP 3依赖的钙释放 和SOCE，经历了戏剧性的变化。IP 3依赖性钙释放增强 几倍，SOCE在减数分裂期间以某种方式失活。确定如何 这些钙信号通路在减数分裂过程中受到调节， 了解钙信号调节。非洲爪蟾的另一个优势 卵母细胞含有钙激活的氯电流， 用作不同钙信号如何影响下游的真实的时间指标 效应器，从而提高我们对钙信号特异性的理解。的 该提案的具体目标是：（1）描述空间和时间特征 IP 3介导的钙释放和SOCE在整个卵子发生过程中的特征; 2） 阐明调节SOCE失活的机制，并增加 在减数分裂期间IP 3介导的释放;和3）记录小鼠卵母细胞中的SOCE，和 测试它在减数分裂期间是否失活。在爪蟾卵母细胞研究中， 钙激活的Cl电流将被测量为下游效应物， 钙信号钙信号传导对于细胞增殖是重要的， 与癌症的发展有关此外，SOCE下调 在原发性免疫缺陷患者的T细胞中，这意味着它是一种 免疫反应中的重要信号通路。因此除了 这项工作有助于更好地了解钙信号传导， 将为钙信号在疾病中的作用提供见解，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.