| Project/Area Number |
13680846
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | Nagasaki University Graduate School of Biomedical Sciences |
|---|
Principal Investigator |
UEZONO Yasuhito Nagasaki Univ. Grad. Sch. Biomed. Sci. Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (20213340)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANIYAMA Kohtaro Nagasaki Univ. Grad. Sch. Biomed. Sci, Professor, 大学院・医歯薬学総合研究科, 教授 (70030898)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | GABA_B receptors / G-protein coupled receptors / Heteromultimerization / Xenopus oocytes / Heterologous expression / FRET / Electrophysiology / Laser confocal microscopy / 内向き整流性Kチャネル / CFTR |
|---|
| Research Abstract |
γ-Amino butyric acids (GABA) is known to act as an inhibitory neurotransmitter on the central and peripheral nervous system. Receptors for GABA are divided into two types : one belongs to ionotropic receptors (GABA_A and GABA_C) and another belongs to metabotoropic G-protein coupled receptors (GABA_B). GABA_B receptor has been cloned in 1997 as a GABA_<B1> receptor and since then, many of works have been focused on the heterologous functional expression of the cloned GABA_B receptors. However, none of the expression study has succeeded. Accordingly the failure of the expression study suggested us the existence of some additional protein(s) for the functional expression of GABA_B receptors. Now functional GABA_B receptors are known to be required to be formed heterodimer with GABA_<B1> and GBA_<B2> receptors.
In the present study we focused on how functional GABA_B receptors are constructed as heterodimer and how the receptors are trafficked to the cell membrane, by the use of multiple assay systems. We found that functional GABA_B receptors are already formed before trafficked to cell membranes. We also found that GABA_<B1> receptors are required for their ligand binding while GABA_<B2> receptors are indispensable for their intracellular signaling through heteromeric G proteins.
We are still in progress of our study and hope to continue to clarify the mechanism how GABA_B receptors are formed and why GABA_B receptors are required to be heteromultimer for their functional expression.
|
