Molecular mechanisms of adiponectin signaling and PAQR function

脂联素信号传导和 PAQR 功能的分子机制

• 批准号: 9349368
• 负责人: Andrew Kruse
• 金额: $ 42.38万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9349368
• 关键词: Address; Affinity; Agonist; Alpha Cell; Animal Model; Antibodies; Area; Attention; Bacteria; Binding; Biochemical; Biological; Biology; Cardiovascular Diseases; Cell membrane; Cells; Cellular Assay; Ceramidase; Ceramides; Complex; Crystallization; Crystallography; Data; Development; Diabetes Mellitus; Diabetic mouse; Drug usage; Engineering; Environment; Enzymes; Event; Exhibits; Family; Family member; Genetic Screening; Genetic study; Goals; Hormones; Human; Hydrolysis; Integral Membrane Protein; Ligand Binding; Ligands; Lipids; Mediating; Membrane; Metabolic; Methods; Molecular; Mus; Neurotransmitters; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organism; Pathway interactions; Phase; Play; Production; Protein Engineering; Proteins; Reagent; Receptor Signaling; Research; Resolution; Role; Second Messenger Systems; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Molecule; Sphingosine; Structure; Therapeutic Uses; Variant; Work; Yeasts; adiponectin; cardiovascular health; cytokine; design; high throughput screening; insulin sensitivity; insulin sensitizing drugs; new therapeutic target; overexpression; public health relevance; receptor; small molecule; targeted treatment; therapeutic development; tool

 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.

 描述(申请人提供)：跨膜信号在所有生物学中发挥核心作用，使细胞能够感知并对环境做出反应。在人类中，完整的膜受体介导激素、神经递质、细胞因子和许多其他信号分子的影响。PAQR受体是一个特性不佳的跨膜受体家族，发现于从细菌到人类的各种生物体中。最近，两个PAQR受体引起了特别的关注，因为它们介导了一种名为脂联素的蛋白质激素的作用。脂联素已被证明在糖尿病和心血管疾病的小鼠模型中具有深刻的胰岛素增敏和心脏保护作用，但对脂联素信号的分子机制知之甚少。为了揭示脂联素受体信号的分子细节，我们将结合脂联素及其受体的结构和生化研究，长期目标是通过脂联素受体和更广泛的PAQR家族来发展对信号的详细分子理解。