G Protein signaling at the endosome

内体中的 G 蛋白信号传导

• 批准号: 7408113
• 负责人: Henrik G. Dohlman
• 金额: $ 37.15万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7408113
• 关键词: Affinity; Animal Behavior; Behavior; Binding; Brain; Cell Surface Receptors; Cell membrane; Cell surface; Cells; Characteristics; Complex; Copper; Cytoplasm; Data; Developed Countries; Dissociation; Drug Addiction; Eating; Employee Strikes; Endosomes; Eukaryota; Eukaryotic Cell; Event; Feeding behaviors; Figs - dietary; Food; Functional disorder; Fungal Genome; GTP Binding; GTP-Binding Proteins; Genomics; Green Fluorescent Proteins; Guanine Nucleotide Exchange Factors; Guanine Nucleotides; Guanosine Triphosphate Phosphohydrolases; Health; Heart Diseases; Hormones; Human; Hypothalamic structure; Intracellular Second Messenger; Lateral; Light; Link; Malignant Neoplasms; Maps; Mediating; Mediator of activation protein; Metabolic; Mitogen-Activated Protein Kinases; Modeling; Molecular; Molecular Conformation; Monitor; Motivation; Nature; Neuropeptides; Neurotransmitters; Nucleus Accumbens; Obesity; Partner in relationship; Pathway interactions; Peripheral; Pheromone; Pheromone Receptors; Phosphatidylinositols; Phospholipids; Phosphoproteins; Phosphotransferases; Physiological; Point Mutation; Prevalence; Production; Protein Overexpression; Proteins; Receptor Signaling; Recruitment Activity; Relative (related person); Research; Research Personnel; Rewards; Role; Second Messenger Systems; Series; Signal Pathway; Signal Transduction; Site; Source; Structure; System; Testing; Transducers; Ursidae Family; WD Repeat; Yeasts; drug reward; melanin-concentrating hormone; melanin-concentrating hormone receptor; mutant; novel; phosphatidylinositol 3-phosphate; programs; protein function; receptor; receptor binding; research study; response; rho; second messenger; yeast protein

DESCRIPTION (provided by applicant): The prevalence of obesity is increasing in most industrialized nations and is a primary cause of significant health complications, such as heart disease and cancer. At the source of the problem is our inability to control food intake when presented with excess food. It is critical that we understand how reward and motivation circuits of the brain regulate food intake and the nature of the dysfunction that causes obesity. While research has identified the hypothalamus as a critical mediator of peripheral metabolic signals, it is not clear how this is converted into the act of eating. This proposal focuses on a hypothalamic neuropeptide called melanin-concentrating hormone (MCH). MCH is produced in the lateral hypothalamus, a region that has been historically associated with rewarding behavior. Moreover, the MCH receptor is expressed in the nucleus accumbens, a region also studies for reward and drug addiction. Preliminary data is presented to demonstrate that MCH signals to the nucleus accumbens to regulated feeding behavior. Experiments are proposed to elucidate the cellular and molecular effects of MCH receptor signaling in the nucleus accumbens using genomic and phosphoprotein analysis. The results from the proposed experiments will shed light on mechanisms of MCH action in the nucleus accumbens while also serving to provide a better molecular explanation of how neuropeptides regulate complex animal behaviors such as food intak.

描述（由申请人提供）：在大多数工业化国家，肥胖的患病率正在上升，并且是导致心脏病和癌症等重大健康并发症的主要原因。问题的根源是当我们面对过量的食物时，我们无法控制食物的摄入量。至关重要的是，我们要了解大脑的奖励和动机回路是如何调节食物摄入的，以及导致肥胖的功能障碍的本质。虽然研究已经确定下丘脑是外周代谢信号的关键媒介，但尚不清楚这是如何转化为进食行为的。这一建议的重点是下丘脑神经肽称为黑色素浓缩激素（MCH）。MCH产生于外侧下丘脑，这个区域历来与奖励行为有关。此外，MCH受体在伏隔核中表达，该区域也研究奖励和药物成瘾。初步数据表明，MCH信号对伏隔核的摄食行为有调节作用。本研究拟利用基因组学和磷酸化蛋白分析来阐明MCH受体信号在伏隔核中的细胞和分子作用。实验结果将揭示MCH在伏隔核中的作用机制，同时也为神经肽如何调节复杂的动物行为（如食物摄入）提供更好的分子解释。