Compartmentation of cAMP and Its Coupling to Epac

我们的研究目的是阐明在细胞内建立cAMP区室化的机制， 控制信号传导特异性以及确定cAMP微结构域的功能重要性。 cAMP通过偶联下游效应物如cAMP依赖性细胞因子介导许多细胞过程。 蛋白激酶（PKA）和由cAMP直接激活的交换蛋白（Epac）。因为cAMP的产生 在不同的亚细胞位点，并迅速扩散到整个细胞，机制必须调节信号 细胞增殖以实现期望的细胞应答。然而，直到最近， 可以有效地探索这些控制机制。受损的cAMP信号传导具有临床意义 肥胖症和II型糖尿病的影响。因此，更好地理解cAMP信号传导可能 从而为这些临床病症带来新的治疗方法。我们研究的具体目的是 进一步开发和表征基于FRET的cAMP指标，以阐明 β-肾上腺素能受体信号传导，并使用这些指标和体外试验来确定下游 线粒体cAMP的作用和功能意义。

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.