Defective survival of naive CD8+ T lymphocytes in the absence of the β3 regulatory subunit of voltage-gated calcium channels

被引：53
作者：
Jha, Mithilesh K. [1 ]
Badou, Abdallah [2 ]
Meissner, Marcel [3 ]
McRory, John E. [4 ]
Freichel, Marc [3 ]
Flockerzi, Veit [3 ]
Flavell, Richard A. [1 ,5 ]
机构：
[1] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
[2] Univ Cadi Ayyad, Fac Polydisciplinaire Safi, Safi, Morocco
[3] Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, D-6650 Homburg, Germany
[4] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada
[5] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA
来源：
NATURE IMMUNOLOGY | 2009年 / 10卷 / 12期
基金：
加拿大健康研究院; 新加坡国家研究基金会;
关键词：
CELL-ACTIVATION; CA2+ CHANNELS; MICE LACKING; PORE SUBUNIT; CRAC CHANNEL; FILAMIN-A; MEMBRANE; TRANSCRIPTION; SIGNAL; CALCINEURIN;
D O I：
10.1038/ni.1793
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
The survival of T lymphocytes requires sustained, Ca2+ influx-dependent gene expression. The molecular mechanism that governs sustained Ca2+ influx in naive T lymphocytes is unknown. Here we report an essential role for the beta 3 regulatory subunit of voltage-gated calcium (Ca-v) channels in the maintenance of naive CD8(+) T cells. Deficiency in beta 3 resulted in a profound survival defect of CD8(+) T cells. This defect correlated with depletion of the pore-forming subunit Ca(v)1.4 and attenuation of T cell antigen receptor (TCR)-mediated global Ca2+ entry in CD8(+) T cells. Ca(v)1.4 and beta 3 associated with T cell signaling machinery and Ca(v)1.4 localized in lipid rafts. Our data demonstrate a mechanism by which Ca2+ entry is controlled by a Ca(v)1.4-beta 3 channel complex in T cells.
引用
收藏
页码：1275 / U7
页数：9
相关论文
共 46 条
  • [1] Critical role for the β regulatory subunits of Cav channels in T lymphocyte function
    Badou, Abdallah
    Jha, Mithilesh Kumar
    Matza, Didi
    Mehal, Wajahat Z.
    Freichel, Marc
    Flockerzi, Veit
    Flavell, Richard A.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (42) : 15529 - 15534
  • [2] Calcium signalling: Dynamics, homeostasis and remodelling
    Berridge, MJ
    Bootman, MD
    Roderick, HL
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (07) : 517 - 529
  • [3] The I-II loop of the Ca2+ channel α1 subunit contains an endoplasmic reticulum retention signal antagonized by the β subunit
    Bichet, D
    Cornet, V
    Geib, S
    Carlier, E
    Volsen, S
    Hoshi, T
    Mori, Y
    De Waard, M
    [J]. NEURON, 2000, 25 (01) : 177 - 190
  • [4] Membrane targeting of L-type calcium channels -: Role of palmitoylation in the subcellular localization of the β2a subunit
    Chien, AJ
    Gao, TY
    Perez-Reyes, E
    Hosey, MM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (36) : 23590 - 23597
  • [5] Autoregulation of NFATc1/A expression facilitates effector T cells to escape from rapid apoptosis
    Chuvpilo, S
    Jankevics, E
    Tyrsin, D
    Akimzhanov, A
    Moroz, D
    Jha, MK
    Luehrmann, JS
    Santner-Nanan, B
    Feoktistova, E
    König, T
    Avots, A
    Schmitt, E
    Berberich-Siebelt, F
    Schimpl, A
    Serfling, E
    [J]. IMMUNITY, 2002, 16 (06) : 881 - 895
  • [6] Cav1.4 encodes a calcium channel with low open probability and unitary conductance
    Doering, CJ
    Hamid, J
    Simms, B
    McRory, JE
    Zamponi, GW
    [J]. BIOPHYSICAL JOURNAL, 2005, 89 (05) : 3042 - 3048
  • [7] Modified Cav1.4 Expression in the Cacna1fnob2 Mouse Due to Alternative Splicing of an ETn Inserted in Exon 2
    Doering, Clinton J.
    Rehak, Renata
    Bonfield, Stephan
    Peloquin, Jean B.
    Stell, William K.
    Mema, Silvina C.
    Sauve, Yves
    McRory, John E.
    [J]. PLOS ONE, 2008, 3 (07):
  • [8] Signal Transduction-Receptors, Mediators, and Genes
    Entschladen, Frank
    Lindquist, Jonathan A.
    Serfling, Edgar
    Thiel, Gerald
    Kieser, Arnd
    Giehl, Klaudia
    Ehrhardt, Christina
    Feller, Stephan M.
    Ullrich, Oliver
    Schaper, Fred
    Janssen, Ottmar
    Hass, Ralf
    Friedrich, Karlheinz
    [J]. SCIENCE SIGNALING, 2009, 2 (63)
  • [9] Gene regulation mediated by calcium signals in T lymphocytes
    Feske, S
    Giltnane, J
    Dolmetsch, R
    Staudt, LM
    Rao, A
    [J]. NATURE IMMUNOLOGY, 2001, 2 (04) : 316 - 324
  • [10] Calcium signalling in lymphocyte activation and disease
    Feske, Stefan
    [J]. NATURE REVIEWS IMMUNOLOGY, 2007, 7 (09) : 690 - 702
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