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学科主题: 药学
题名:
Amplification and propagation of pacemaker Ca2+ signals by cyclic ADP-ribose and the type 3 ryanodine receptor in T cells
作者: Kunerth, S1; Langhorst, MF1; Schwarzmann, N1; Gu, XF1; Huang, LJ1; Yang, ZJ1; Zhang, LR1; Mills, SJ1; Zhang, LH1; Potter, BVL1; Guse, AH1
关键词: Ca2+ signaling ; ryanodine receptor ; cyclic ADP-ribose ; T cell ; D-myo-inositol 1,4,5-trisphosphate receptor
刊名: JOURNAL OF CELL SCIENCE
发表日期: 2004-04-15
DOI: 10.1242/jcs.01063
卷: 117, 期:10, 页:2141-2149
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR ; CALCIUM-RELEASE ; SKELETAL-MUSCLE ; MYOINOSITOL 1,4,6-TRISPHOSPHOROTHIOATE ; ELEMENTARY EVENTS ; PARTIAL AGONISTS ; LYMPHOCYTES ; TRISPHOSPHATE ; MECHANISMS ; MYOCYTES
英文摘要:

Ligation of the T-cell receptor/CD3 complex results in global Ca2+ signals that are essential for T-cell activation. We have recently reported that these global Ca2+ signals are preceded by localized pacemaker Ca2+ signals. Here, we demonstrate for the first time for human T cells that an increase in signal frequency of subcellular pacemaker Ca2+ signals at sites close to the plasma membrane, in the cytosol and in the nucleus depends on the type 3 ryanodine receptor (RyR) and its modulation by cyclic ADP-ribose. The spatial distribution of D-myo-inositol 1,4,5-trisphosphate receptors and RyRs indicates a concerted action of both of these receptors/Ca2+ channels in the generation of initial pacemaker signals localized close to the plasma membrane. Inhibition or knockdown of RyRs resulted in significant decreases in (1) the frequency of initial pacemaker signals localized close to the plasma membrane, and (2) the frequency of localized pacemaker Ca2+ signals in the inner cytosol. Moreover, upon microinjection of cyclic ADP-ribose or upon extracellular addition of its novel membrane-permeant mimic N-1-ethoxymethyl-substituted cyclic inosine diphosphoribose, similarly decreased Ca2+ signals were observed in both type 3 RyR-knockdown cells and in control cells microinjected with the RyR antagonist Ruthenium Red. Taken together, our results show that, under physiological conditions in human T cells, RyRs play crucial roles in the local amplification and the spatiotemporal development of subcellular Ca2+ pacemaker signals.

语种: 英语
WOS记录号: WOS:000221607600028
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53090
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Univ Hosp Hamburg Eppendorf, Ctr Med Expt, Inst Biochem & Mol Biol 1, D-20246 Hamburg, Germany
2.Peking Univ, Natl Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
3.Univ Bath, Dept Pharm & Pharmacol, Wolfson Lab Med Chem, Bath BA2 7AY, Avon, England

Recommended Citation:
Kunerth, S,Langhorst, MF,Schwarzmann, N,et al. Amplification and propagation of pacemaker Ca2+ signals by cyclic ADP-ribose and the type 3 ryanodine receptor in T cells[J]. JOURNAL OF CELL SCIENCE,2004,117(10):2141-2149.
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