Compartmentation of cAMP and Its Coupling to Epac

我们研究的目标是阐明在脑内建立cAMP区划的机制。 控制信号的特异性以及决定cAMP微域的功能重要性。 CAMP通过偶联到下游效应分子，如cAMP依赖，介导许多细胞过程 蛋白激酶(PKA)和cAMP直接激活的交换蛋白(EPAC)。因为夏令营的产生 在不同的亚细胞位置，并在细胞内迅速扩散，机制必须调节信号 传播以达到所需的细胞响应。然而，直到最近，工具才成为 可以有效地探索这些控制机制。CAMP信号受损有临床意义 例如肥胖症和II型糖尿病。因此，对cAMP信号的更好理解可能 为这些临床疾病带来新的治疗方法。我们研究的具体目的是 进一步开发和表征基于FRET的cAMP指示剂，以阐明 β-肾上腺素能受体信号转导，并利用这些指标和体外分析来确定下游 线粒体cAMP的效应因子及其功能意义。

The goal of our research is to elucidate the mechanisms that establish cAMP compartmentation in controlling signaling specificity as well as determine the functional importance of cAMP microdomains. cAMP mediates many cellular processes by coupling to downstream effectors such as cAMP dependent protein kinase (PKA) and exchange protein directly activated by cAMP (Epac). Because cAMP is produced at distinct subcellular sites and diffuses rapidly throughout the cell, mechanisms must regulate signal propagation in order to achieve a desired cellular response. However, only recently have tools become available to effectively explore these mechanisms of control. Impaired cAMP signaling has clinical implications such as obesity and type II diabetes. Therefore, a better understanding of cAMP signaling may lead to new therapeutic approaches for these clinical conditions. The specific aims of our reseach are to further develop and characterize FRET-based cAMP indicators to elucidate the spatiotemporal dynamics of beta-adrenergic receptor signaling and use these indicators and in vitro assaysto determine the downstream effectors and functional significance of mitochondrial cAMP.