抄録
Store-operated calcium entry (SOCE) or calcium release-activated calcium current (ICRAC) is a critical pathway to replenish intracellular calcium stores, and plays indispensable roles in cellular functions such as antigen-induced T lymphocyte activation. Despite the importance of ICRAC in cellular functions, lack of potent and specific inhibitor has limited the approaches to the function of ICRAC in native cells. 2-Aminoethyl diphenylborinate (2-APB) is a widely used SOCE/ICRAC inhibitor, while its effect is rather unspecific. In the attempt to develop more potent and selective compounds here we identified two structurally isomeric 2-APB analogues that are 100-fold more potent than 2-APB itself. One of the 2-APB analogues activates and inhibits endogenous SOCE depending on the concentration while the other only inhibits it. The 2-APB analogue inhibits store depletion-mediated STIM1 clustering as well as heterologously expressed CRAC current. Together with the observation that, unlike 2-APB, the analogue compounds failed to activate CRACM3/Orai3 current in the absence of STIM, our results suggest that inhibition and activation of SOCE/ICRAC by the 2-APB analogues is mediated by STIM.
本文言語 | English |
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ページ(範囲) | 1-10 |
ページ数 | 10 |
ジャーナル | Cell Calcium |
巻 | 47 |
号 | 1 |
DOI | |
出版ステータス | Published - 2010 1月 |
外部発表 | はい |
ASJC Scopus subject areas
- 細胞生物学
- 分子生物学
- 生理学