| Project/Area Number |
17500259
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | HIROSHIMA UNIVERSITY (2006)
Saitama Medical University (2005) |
|---|
Principal Investigator |
SAITO Yumiko Hiroshima University, Graduate School of Integrated Arts and Sciences, Professor, 大学院総合科学研究科, 教授 (00215568)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Kei Saitama Medical School, faculty of medicine, Professor, 医学部, 教授 (30211577)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | feeding / depression / anxiety / signal transduction / G protein / 不安 / 肥満 / 受容体 / 細胞内情報伝達 / うつ |
|---|
| Research Abstract |
Melanin-concentrating hormone (MCH) receptor 1 (MCH1R) is a class A G protein-coupled receptor (GPCR). The MCH system has been linked to a variety of physiological functions, including the regulation of feeding, energy metabolism and stress-induced responses. We have already reported the importance of a dibasic motif in the membrane-proximal C-terminal region for MCH1R function. In this project, we further reveal that an Arg residue in intracellular loop 2 of MCH1R (R155) plays a critical role in receptor function. To purify potential MCH1R interacting proteins from mouse brain, the N-terminus, second intracellular loop (i2), third intracellular loop (i3) or the C terminal tail was expressed as a GST fusion protein and immobilized on glutathione-agarose. MALDI-TOF-MS analysis identified several proteins, and one of protein preferentially interacted with i2 domain was found to belong to Ser/Thr kinase family. In 293T cells that were transiently transfected with MCH1R and the kinase, stimulation of MCH1R by agonist results in the recruitment of the activated kinase from cytoplasm to the plasma membrane, in which the kinase was colocalized with MCH1R. A well-characterized inhibitor for the kinase did significantly interfere MCH-induced internalization. This is the first protein-protein interaction demonstrated to alter agonist-stimulated internalization of the MCH1R.
|
