G Protein signaling at the endosome

内体中的 G 蛋白信号传导

基本信息

批准号：
7250443
负责人：
Henrik G. Dohlman
金额：
$ 29.14万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
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/7250443
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

项目摘要

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，肥胖症的患病率正在增加，并且是导致心脏病和癌症等严重健康并发症的主要原因。问题的根源在于我们在吃过量的食物时无法控制食物的摄入量。了解大脑的奖赏和动机回路如何调节食物摄入以及导致肥胖的功能障碍的性质至关重要。虽然研究已确定下丘脑是外周代谢信号的关键调节者，但尚不清楚其如何转化为饮食行为。该提案的重点是一种称为黑色素浓缩激素（MCH）的下丘脑神经肽。 MCH 产生于下丘脑外侧，该区域历来与奖励行为相关。此外，MCH 受体在伏隔核中表达，该区域也研究奖赏和药物成瘾。初步数据表明 MCH 向伏隔核发出信号以调节进食行为。实验旨在利用基因组和磷蛋白分析来阐明伏隔核中 MCH 受体信号传导的细胞和分子效应。拟议实验的结果将揭示伏隔核中 MCH 作用的机制，同时也有助于为神经肽如何调节食物摄入等复杂的动物行为提供更好的分子解释。