2010 Fiscal Year Final Research Report
Identification of the regulating molecules for the melanin-concentrating hormone receptor 1 that is specifically involved in feeding and depression.
| Project/Area Number |
20500337
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Hiroshima University |
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Principal Investigator |
SAITO Yumiko Hiroshima University, 大学院・総合科学研究科, 教授 (00215568)
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| Project Period (FY) |
2008 – 2010
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| Keywords | G蛋白質共役型受容体 / 摂食 / 細胞内情報伝達 / 構造活性相関 |
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| Research Abstract |
Melanin-concentrating hormone receptor 1 (MCHR1) is a G protein-coupled receptor (GPCR) that is highly expressed in the central nervous system. Extensive 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 analyzing the effect of a series of site-directed mutations of rat MCHR1 on receptor conformational changes, we found that DRY in i2 loop and Phe318 in helix 8 of MCHR1 are the structurally critical site for receptor dynamics. We further identified three RGS proteins that negatively modulated MCHR1-mediated signaling by acting as GTPase-activating manner. These results will help to better understand the complex mechanism for MCHR1 activation.
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