Novel ion channel functions utilizing protein-protein interactions
| Project/Area Number |
15390060
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General physiology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
FURUKAWA Tetsushi Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (80251552)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KIMURA Akinori Tokyo Medical and Dental University, Medical research Institute, Professor, 難治疾患研究所, 教授 (60161551)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2003: ¥5,000,000 (Direct Cost: ¥5,000,000)
|
|---|
| Keywords | protein-protein interaction / potassium channel / phosphorylation / long QT syndrome / nitric oxide / caveola / calmodulin / gender-difference / イオンチャネル / 心血管系細胞 / ジェンダー / 不整脈 / ニトロ化 / カベオリン3 / 一酸化窒素(NO) / mechano-electrical feedback / 性ホルモン / non-genomic pathway / 漢方薬 |
|---|
| Research Abstract |
To efficiently transmit various extra-cellular and intra-cellular signals, ion channels form macro-molecular complex with various proteins. In the previous research grant (2003-2004, project number 13670035), we have performed comprehensive screening of proteins interacting with various ion channels. And, we identified more than 10 novel protein-protein interactions involving ion channels. In the present grant, we carried out continuous effort to unveil novel ion channel functions that utilize identified protein-protein interactions.
We identified novel ion channel regulatory system using nitric oxide (NO). NO is originally identified as a endothelial-derived relaxing factor (EDRF), and plays a very important role in cardiovascular system. NO is a gaseous signal molecule that is diffusible and easy to be oxidized. Thus, to achieve specific protein regulation, NO-producing system (NO synthase ; NOS) should be in the vicinity of target proteins, ion channels in this case. Thus, protein-protein interaction involving NOS and ion channels turns out to be intriguing research target.
We demonstrated that L-type Ca^<2+> channel current (I_<ca,L>) and delayed rectifier K^+ current (I_<Ks>) are regulatory target of NO. I_<Ca,L> is inhibited by NO in a cGMP-dependent manner, while I_<KS> is activated in a cGMP-independent manner, most likely by s-nitrosylation of cysteine thiol residue. We demonstrated that these novel ion channel regulatory system plays a crucial role in several cellular phenomenon, including (1) fine-tuning of Ca^<2+> -entry ; (2) non-genomic regulation of ion channels by sex hormones ; (3) mechanisms of actions of herbal medicine ; and (4) innate immunity.
We strongly believe that we should extend these findings to establish ion channel regulation by s-nitrosylation in cardiovascular system, and to develop new strategies for treatment of arrhythmias, life-style related diseases, and other common diseases in the elderly.
|
Report
(4 results)
Research Products
(15 results)
-
-
-
-
-
-
-
-
-
-
[Journal Article] Aquaporin-2 trafficking is regulated by PDZ-domain containing protein SPA-1.2004
Author(s)
Noda Y, Horikawa S, Furukawa T, Hirai K, Katayama Y, Asai T, Kuwahara M, Katagiri K, Kinashi T, Hattori M, Minato N, Sasaki S.
-
Journal Title
FEBS Letters. 568(1-3)
Pages: 139-145
Related Report
-
-
-
-
-
[Publications] Yoneda, K., Furukawa, T., Zheng, Y.-J., Momoi, T., Inagaki, N., et al.: "An autocrine/paracrine loop linking keratin 14 aggregates to TNFa-mediated cytotoxicity in a keratinocyte model of epidermolysis bullosa simplex."J.Biol.Chem. (in press).
