論文 - 詳細
| RRC ID | 43390 |
|---|---|
| 著者 | Tojyo Y, Morita T, Nezu A, Tanimura A. |
| タイトル | The clustering of inositol 1,4,5-trisphosphate (IP(3)) receptors is triggered by IP(3) binding and facilitated by depletion of the Ca(2+) store. |
| ジャーナル | J Pharmacol Sci |
| Abstract |
The inositol 1,4,5-trisphosphate receptors (IP(3)Rs) form clusters following agonist stimulation, but its mechanism remains controversial. In this study, we visualized the clustering of green fluorescent protein (GFP)-tagged type 3 IP(3)R (GFP-IP(3)R3) in cultured living cells using confocal microscopy. Stimulation with ATP evoked GFP-IP(3)R3 clustering not only in cells with replete Ca(2+)-stores but also in cells with depleted Ca(2+) stores. Thapsigargin (ThG) and ionomycin failed to mimic the ATP-induced cluster formation despite the continuous elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)). Application of IP(3) caused GFP-IP(3)R3 clustering in permeabilized cells, and the response was completely inhibited by heparin, a competitive inhibitor of IP(3)R. Experiments using LIBRAv, an IP(3) biosensor, showed that ATP significantly stimulated IP(3) generation even in store-depleted cells. We also found that pretreatment with ThG accelerated or enhanced the ATP-induced clustering in both the presence and absence of extracellular Ca(2+). When permeabilized cells were stimulated with the threshold of IP(3), the GFP-IP(3)R3 clustering clearly occurred in Ca(2+)-free medium but not in Ca(2+)-containing medium. These results strongly support the hypothesis that the agonist-induced clustering of IP(3)R is triggered by IP(3) binding, rather than [Ca(2+)](i) elevation. Although depletion of the Ca(2+) store by itself does not cause the clustering, it may increase the sensitivity of IP(3)R to cluster formation, leading to facilitation of IP(3)-triggered clustering. |
| 巻・号 | 107(2) |
| ページ | 138-50 |
| 公開日 | 2008-6-1 |
| DOI | 10.1254/jphs.08021fp |
| PII | JST.JSTAGE/jphs/08021FP |
| PMID | 18544901 |
| MeSH | Adenosine Triphosphate / pharmacology Animals COS Cells Calcium / metabolism* Chlorocebus aethiops Inositol 1,4,5-Trisphosphate / metabolism* Inositol 1,4,5-Trisphosphate Receptors / metabolism* |
| IF | 2.835 |
| 引用数 | 17 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | COS-7(RCB0539) |