BFGF AND CELL CONTACT REGULATE GRANULOSA CELL APOPTOSIS

描述（改编自研究者摘要）：该提案是 分为七个具体目标。 该提案的总体目标是 确定控制颗粒细胞活力的细胞机制。 的 研究人员已经得出初步数据， 生长因子，通过旁分泌或自分泌机制起作用，细胞 接触相互作用以调节颗粒细胞活力。 单元接触 这一机制的一部分似乎是通过N-钙粘蛋白介导的，而不是通过 间隙连接蛋白。 有趣的是，研究人员已经产生了 初步数据表明，N-钙粘蛋白与受体相互作用， bFGF。 这一观察结果表明，粘附分子可以调节细胞的生长， 通过改变通过生长因子受体的信号转导的存活力。 这是生物学中一个有趣的普遍原则，值得更多的关注。 详细调查。 如上所述，该提案分为7个具体目标。 在特定 目的1，研究者将确定是否合成肽（LRAHAVDVNG）， 来源于细胞外结构域中发现的氨基酸序列 FGF受体和N-cadherin的结合减弱了bFGF诱导 颗粒细胞聚集并维持颗粒细胞活力。 在 具体目标2，研究者计划确定N-钙粘蛋白 抗体阻止bFGF与其受体结合。 具体目标3中， 研究者将确定bFGF是否与其受体结合并导致 形成N-钙粘蛋白/FGF受体复合物。 具体目标4： 研究者将确定N-钙粘蛋白抗体是否减弱bFGF 以刺激其受体的酪氨酸磷酸化以及其他 proteins. 在具体目标5中，研究者将确定N-钙粘蛋白 抗体破坏颗粒细胞的肌动蛋白细胞骨架， 诱导凋亡而不改变蛋白酪氨酸或在改变蛋白酪氨酸之前 磷酸化 在具体目标6中，研究者将确定bFGF是否 减少颗粒细胞凋亡并诱导颗粒细胞聚集， 调节酪氨酸磷酸化状态的表达和/或细胞内酪氨酸磷酸化状态的表达， N-钙粘蛋白和相关连环蛋白的定位。 在具体目标7中， 研究者将测定bFGF，FGF受体， 闭锁和非闭锁卵泡中的N-钙粘蛋白和连环蛋白。 的 研究人员希望这些研究将提供新的见解， bFGF和颗粒接触相互作用的细胞机制， 调节颗粒细胞活力。

DESCRIPTION (Adapted from the Investigator's Abstract): The proposal is divided into 7 specific aims. The overall goal of the proposal is to identify the cellular mechanisms that control granulosa cell viability. The investigator has generated preliminary data that both basic fibroblast growth factor, acting through a paracrine or autocrine mechanism and cell contact interact to regulate granulosa cell viability. The cell contact component of this mechanism appears to be mediated via N--cadherin, not by gap junction proteins. Interestingly, the investigators have generated preliminary data which suggests N-cadherin interacts with the receptor for bFGF. This observation suggests that adhesion molecules may modulate cell viability by altering signal transduction through growth factor receptors. This is an interesting general principle in biology which deserves more detailed investigation. As noted above, the proposal is divided into 7 specific aims. In Specific Aim 1, the investigator will determine if a synthetic peptide (LRAHAVDVNG), derived from an amino acid sequence found within the extracellular domains of both the FGF receptor and N-cadherin attenuates bFGF's ability to induce granulosa cell aggregation and maintain granulosa cell viability. In Specific Aim 2, the investigator plans to determine if the N-cadherin antibody prevents bFGF from binding to its receptor. In Specific Aim 3, the investigator will determine if bFGF binds to its receptor and causes the formation of an N-cadherin/FGF receptor complex. In Specific Aim 4, the investigator will determine if N-cadherin antibody attenuates bFGF's ability to stimulate tyrosine phosphorylation of its receptor as well as other proteins. In Specific Aim 5, the investigator will determine if N-cadherin antibody disrupts the actin cytoskeleton of the granulosa cell and thereby induces apoptosis without or prior to altering protein tyrosine phosphorylation. In Specific Aim 6, the investigator will determine if bFGF reduces granulosa cell apoptosis and induces granulosa cell aggregation by regulating the expression of tyrosine phosphorylation status and/or cellular localization of N-cadherin and the associated catenins. In Specific Aim 7, the investigator will determine the protein levels of bFGF, FGF receptor, N-cadherin, and catenins in atretic and non-atretic follicles. The investigator hopes that these studies will provide new insights into the cellular mechanism through which bFGF and granulosa contact interact to regulate granulosa cell viability.