| Project/Area Number |
15500262
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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 | Nagasaki University |
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Principal Investigator |
UEZONO Yasuhito Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20213340)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBUYA Izumi University of Occupational and Environmental Health, School of Medicine, Associate Professor, 医学部, 助教授 (50162649)
TANIYAMA Kohtaro Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (70030898)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | GABA_B receptor / G protein-coupled receptors / Heterodimerization / Xenopus oocyte / FRET / Heterologous expression / Electrophyslology / Confocal Laser Microscopy / GABA-B受容体 / heterodimerization / heterolopous expression / 共焦点レーザー顕微鏡 |
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| Research Abstract |
GABA is known to act as an inhibitory neurotransmitter on the central and peripheral nervous system. One of GABA receptors, the metabotropic GABAB receptor has been cloned in 1998. Functional GABA_B receptors are required to be formed with two GABAB receptor subunits, GABAB1 and GABAB2. Recent progress has also shown that not GABAB receptors but also many types of GPCRs such as μ- and δ-opioid receptors form heterodimer. Further, properties of such heterodimeric receptors have been reported to be differed from their parental monomeric receptors. However, nothing is known how heterodimers are formed and none of the compounds have been identified that modify the heterodimerization of GPCRs.
In the present study we focused on identification of factors that modify either formation of the heterodimerized GPCRs or trafficking of heterodimerized GPCR to the cell surface.
Our results showed that heterodimerization of GPCRs already occurred in the Golgi or endoplasmic reticulum and then heterodimer formed there were trafficked to cell surface. In addition we demonstrated that geldanamycin, an inhibitor of HSP90, which acts as chaperone in the cells, inhibited the trafficking of the heterodimerized receptors to the cells as well as formation of heterodimerization. These results indicated that some protein chaperone such as HSP 90 could be involved in the formation, and trafficking of the heterodimerized receptors to the cell surface.
We are now searching for compounds that modify formation and trafficking of the heterodimerized receptors. Such compounds will shed lights to open new category of drugs for modification of GPCR dimerization.
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