| Project/Area Number |
20790093
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | National Center of Neurology and Psychiatry |
|---|
Principal Investigator |
ICHIKAWA Daiju National Center of Neurology and Psychiatry, 神経研究所 免疫研究部, 流動研究員 (60462793)
|
|---|
| Project Period (FY) |
2008 – 2009
|
| Project Status |
Completed (Fiscal Year 2009)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 免疫学 / T細胞アナジー / GRAIL / 免疫寛容 / 細胞骨格 / 自己免疫 / E3リガーゼ |
|---|
| Research Abstract |
The molecular basis of cell-intrinsic program that establishes T cell anergy is not completely understood. Recent reports demonstrated that E3 ubiquitin ligases, including gene related to anergy in lymphocytes (GRAIL), as essential components to induce and maintain T-cell anergy. The aim of this study is identification of GRAIL E3 ligase substrates to substantiate the molecular mechanisms of T cell anergy. We identified 30 proteins specifically decreased under anergic condition as we previously reported. In addtion to RhoGDIα/β, we identified several actin cytoskelton-associated proteins as the substrates of GRAIL. These proteins were ubiquitinated by GRAIL E3 ligase but not enzymatically inactive H2N2 or RING deletion GRAIL. Confocal laser microscopy analysis revealed that these proteins were colocalized with GRAIL. These data demonstrate that GRAIL might regulate actin cytoskelton-associated proteins to maintain an anergic states of T cell.
|
