Molecular ON-OFF mechanisms of ATP-releasing maxi-anion channel opening
| Project/Area Number |
17K19517
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Biomedical structure and function and related fields
|
|---|
| Research Institution | National Institute for Physiological Sciences |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
岡田 俊昭 生理学研究所, 生体機能調節研究領域, 研究員 (00373283)
|
|---|
| Project Period (FY) |
2017-06-30 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
|
|---|
| Keywords | アニオンチャネル / Maxi-Cl / SLCO2A1 / アネキシンA2 / S100A10 / 生理学 / ATP放出 |
|---|
| Outline of Final Research Achievements |
Maxi-anion channel (Maxi-Cl) is ubiquitously expressed and involved in a number of important cell functions especially by serving as an ATP release pathway. We recently identified SLCO2A1 as its essential core component. However, the regulatory component required for the channel activation/inactivation remains unidentified. In the present study, we have elucidated that an actin-binding protein, annexinA2 (ANXA2), confers protein tyrosine dephosphorylation dependence of Maxi-Cl channel by binding to SLCO2A1. Also, we have shown that S100A10, a binding partner of ANXA2, confers intracellular Ca2+ dependence of Maxi-Cl. Thus, it is concluded that AnXA2-S100A10 represents the regulatory component of Maxi-Cl/SLCO2A1 channel which is dependent on protein tyrosine dephosphorylation and intracellular Ca2+.
|
| Academic Significance and Societal Importance of the Research Achievements |
Maxi-Clチャネルは、細胞容積調節、尿細管-糸球体フィードバックや大腸脂肪酸吸収などの生理的過程に関与する重要分子である。そのコア分子としてのSLCO2A1の同定は私達によって2017年に行われたが、その開閉を制御する分子メカニズムは不明であった。本研究ではそれを世界に先駆けて解明した。Maxi-Clチャネルは、虚血および虚血・再灌流時においても活性化され、脳アストロサイトや心筋細胞からのATPやグルタミン酸などの細胞外シグナル分子の放出路を与える。したがって、Maxi-Clのコア分子のみならず今回発見されたその制御分子は、今後、脳・心臓における虚血障害に対する治療標的となる可能性がある。
|
Report
(4 results)
Research Products
(23 results)
-
-
-
[Journal Article] Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform.2020
Author(s)
R. Nakamura, T. Numata, G. Kasuya, T. Yokoyama, T. Nishizawa, T. Kusakizako, T. Kato, T. Hagino, N. Dohmae, M. Inoue, K. Watanabe, H. Ichijo, M. Kikkawa, M. Shirouzu, T.J. Jentsch, R. Ishitani, Y. Okada, O. Nureki
-
Journal Title
Communication Biology
Volume: -
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
