論文 - 詳細
| RRC ID | 72168 |
|---|---|
| 著者 | Horia Vais, Min Wang, Karthik Mallilankaraman, Riley Payne, Chris McKennan, Jeffrey T Lock, Lynn A Spruce, Carly Fiest, Matthew Yan-lok Chan, Ian Parker, Steven H Seeholzer, J Kevin Foskett, Don-On Daniel Mak |
| タイトル | ER-luminal [Ca2+] regulation of InsP3 receptor gating mediated by an ER-luminal peripheral Ca2+-binding protein |
| ジャーナル | eLife |
| Abstract |
Modulating cytoplasmic Ca2+ concentration ([Ca2+]i) by endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate receptor (InsP3R) Ca2+-release channels is a universal signaling pathway that regulates numerous cell-physiological processes. Whereas much is known regarding regulation of InsP3R activity by cytoplasmic ligands and processes, its regulation by ER-luminal Ca2+ concentration ([Ca2+]ER) is poorly understood and controversial. We discovered that the InsP3R is regulated by a peripheral membrane-associated ER-luminal protein that strongly inhibits the channel in the presence of high, physiological [Ca2+]ER. The widely-expressed Ca2+-binding protein annexin A1 (ANXA1) is present in the nuclear envelope lumen and, through interaction with a luminal region of the channel, can modify high-[Ca2+]ER inhibition of InsP3R activity. Genetic knockdown of ANXA1 expression enhanced global and local elementary InsP3-mediated Ca2+ signaling events. Thus, [Ca2+]ER is a major regulator of InsP3R channel activity and InsP3R-mediated [Ca2+]i signaling in cells by controlling an interaction of the channel with a peripheral membrane-associated Ca2+-binding protein, likely ANXA1. |
| 巻・号 | 9 |
| 公開日 | 2020-5-18 |
| DOI | 10.7554/elife.53531 |
| PMID | 32420875 |
| PMC | PMC7259957 |
| MeSH | A549 Cells Animals Annexin A1 / metabolism* Calcium / metabolism* Calcium Signaling / physiology* Calcium-Binding Proteins / metabolism Cell Line, Tumor Cell Physiological Phenomena / physiology Chickens Endoplasmic Reticulum / metabolism* HEK293 Cells Humans Inositol 1,4,5-Trisphosphate / metabolism Inositol 1,4,5-Trisphosphate Receptors / metabolism* Ion Channel Gating Mice Patch-Clamp Techniques Rats |
| IF | 7.08 |
| 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 | X(Twitter) |
| 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 | DT40(RCB1464) IP3R^(-) DT40(RCB1467) |