2010 Fiscal Year Final Research Report
Characterization of novel activator of G protein signalings (AGSs) indentified in the hypertrophic heart.
| Project/Area Number |
20590212
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General physiology
|
|---|
| Research Institution | Yokohama City University |
|---|
Principal Investigator |
SATO Motohiko Yokohama City University, 医学部, 准教授 (40292122)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Satoshi 横浜市立大学, 医学部, 准教授 (60233475)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Keywords | 細胞内情報伝達 / G蛋白質 / 心肥大 |
|---|
| Research Abstract |
In addition to G-protein coupled receptors, there exist receptor-independent regulators for heterotrimeric G-proteins which provide alternative signal input that may be involved in the adaptation process of cells to various stresses. As a part of an effort to identify such entities in cardiovascular diseases, we used a functional screen to identify receptor-independent activators of G-protein signaling (AGS) in the hypertrophied mouse heart by transverse aortic constriction. We identified three MITF/TFE transcription factors, TFE3 as novel AGS proteins for Gα16. TFE3 induced translocation of Gα16 to the nucleus. Interestingly, the accumulation of TFE3/Gα16 in the nucleus induced the expression of claudin 14, which was a key component of membrane structure in cardiomyocytes.TFE3 transcription factor is a new AGS for Gα16, that appears to generate a TEF3/Gα16 complex in the nucleus that drives the transcription of claudin 14. These findings suggest the existence of a novel mechanism of transcriptional regulation under pressure overload stress via the relocalization/activation of Gα subunit with specific AGS proteins.
|
