Molecular and physiological basis of melanin-concentrating hormone receptor expressed in nervous system
| Project/Area Number |
15K06775
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 広島大学, 総合科学研究科, 教授 (00215568)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Gタンパク質共役型受容体 / 構造活性相関 / 一次繊毛 / 摂食 / うつ不安 / RGSタンパク質 / シグナル伝達 / GPCR / 海馬 / ＧＰＣＲ / 1次繊毛 / G蛋白質 |
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| Outline of Final Research Achievements |
Melanin-concentrating hormone receptor 1 (MCHR1) is a neuronal GPCR, which is implicated in the regulation of feeding and emotional processing in rodents. In this study, we first identified two unique MCHR1 mutants, i2_6sub and i3_6sub, which contained six simultaneously substituted residues in i2 loop or a combination of substituted residues in i3 loop and TM5 domain, respectively, selectively reduced Gi/o-sensitive PTX responsiveness. Next, I found a novel biological action of MCH; initiating efficient ciliary shortening in ciliary MCHR1-expressing hRPE1 cells via Gi/o-Akt pathway. Further, we revealed that MCH increases soluble tubulin levels in the cell body, and coordinates actin machinery for MCHR1-mediated cilia shortening. Finally, we established depression-resistant mice overexpressing RGS8. Such behavior may result through RGS8-ciliary MCHR1 interaction in the CA1 region. These results for 3-years will pave the new way for elucidating the physiology of ciliary MCHR1 function.
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Report
(4 results)
Research Products
(45 results)
