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Amplification and propagation of pacemaker Ca2+ signals by cyclic ADP-ribose and the type 3 ryanodine receptor in T cells
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
2004-04-15
DOI10.1242/jcs.01063
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
引用统计
被引频次:30[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53090
专题北京大学药学院
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
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GB/T 7714
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.
APA Kunerth, S.,Langhorst, MF.,Schwarzmann, N.,Gu, XF.,Huang, LJ.,...&Guse, AH.(2004).Amplification and propagation of pacemaker Ca2+ signals by cyclic ADP-ribose and the type 3 ryanodine receptor in T cells.JOURNAL OF CELL SCIENCE,117(10),2141-2149.
MLA Kunerth, S,et al."Amplification and propagation of pacemaker Ca2+ signals by cyclic ADP-ribose and the type 3 ryanodine receptor in T cells".JOURNAL OF CELL SCIENCE 117.10(2004):2141-2149.
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