G Protein signaling at the endosome

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，并且是严重健康并发症（如心脏病和癌症）的主要原因。问题的根源是我们无法控制食物摄入量时，提出了过量的食物。我们必须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介质，但尚不清楚这是如何转化为进食行为的。这项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，这是一个历史上与奖励行为相关的区域。此外，MCH受体表达于丘脑核，该区域也用于研究奖赏和药物成瘾。初步的数据表明，MCH信号到丘脑核调节摄食行为。实验提出了阐明细胞和分子的影响MCH受体信号转导的细胞和分子的核？使用基因组和磷蛋白分析。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复杂的动物行为（例如食物摄入）提供更好的分子解释。

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.