Molecular disection of melanin-concenting hormone receptor 1

黑色素浓缩激素受体1(MCHR1)是一种G蛋白偶联受体，在中枢神经系统中高度表达。许多对基因工程动物和选择性拮抗剂的研究表明，MCHR1在能量稳态和情绪处理等许多生理功能的调节中发挥着重要作用。通过对大鼠MCHR1的广泛的生物学和药理学研究，我们已经完成了(1)建立G蛋白功能获得突变体的三维模型，(2)鉴定了两个对GI敏感但对GQ激活不敏感的突变体，(3)建立了选择性在中枢神经系统过度表达MCHR1结合分子的转基因小鼠，以及(4)从青蛙中克隆了四个MCHR的分子克隆和信号转导途径。我们进一步鉴定了MCHR1的纤毛靶向序列。这些结果将为更好地理解MCHR1在体内激活的复杂机制提供重要信息。

Melanin-concentrating hormone receptor 1 (MCHR1) is a G protein-coupled receptor (GPCR) that is highly expressed in the central nervous system. Many studies of genetically engineered animals and selective antagonists showed an important role of MCHR1 in the regulation of many physiological functions including energy homeostasis and emotional processing. By extensive biological and pharmacological studies of rat MCHR1, we have accomplished that (1) generation of 3D-modeling of gain-of-function mutant with G protein, (2) identification of two mutants that are sensitive for Gi but not for Gq activation, (3) generation of transgenic mice that selectively over express one of MCHR1-binding molecule in the CNS, and (4) molecular cloning and signaling pathway for four MCHR from frog. We further characterized ciliary targeting sequence of MCHR1. These results will provide important information to better understand the complex mechanism for MCHR1 activation in vivo.