Molecular mechanisms of adiponectin signaling and PAQR function

 描述（由申请人提供）：跨膜信号传导在所有生物学中起着核心作用，允许细胞感知和响应其环境。在人类中，整合膜受体介导激素、神经递质、细胞因子和许多其他信号分子的作用。PAQR受体是一个特征不明显的跨膜受体家族，存在于从细菌到人类的生物体中。最近，两种PAQR受体引起了特别的关注，因为它们介导了一种称为脂联素的蛋白质激素的作用。脂联素在糖尿病和心血管疾病小鼠模型中具有显著的胰岛素增敏和心脏保护作用，但脂联素信号转导的分子机制尚不清楚。为了解开脂联素受体信号传导的分子细节，我们将追求脂联素及其受体的结构和生物化学研究的组合，长期目标是通过脂联素受体和更广泛的PAQR家族发展详细的分子理解。

 DESCRIPTION (provided by applicant): Transmembrane signaling plays a central role in all of biology, allowing cells to sense and respond to their environment. In humans, integral membrane receptors mediate the effects of hormones, neurotransmitters, cytokines, and a multitude of other signaling molecules. The PAQR receptors are a poorly characterized family of transmembrane receptors, found in organisms ranging from bacteria to humans. Recently, two PAQR receptors have attracted particular attention because they mediate the effects of a protein hormone called adiponectin. Adiponectin has been shown to induce profound insulin-sensitizing and cardioprotective effects in mouse models of diabetes and cardiovascular disease, but little is known regarding the molecular mechanisms of adiponectin signaling. To unravel the molecular details of adiponectin receptor signaling, we will pursue a combination of structural and biochemical studies of adiponectin and its receptors, with the long term goal of developing a detailed molecular understanding of signaling through the adiponectin receptors and broader PAQR family.